Novel Heterocyclic Derivatives Useful as SHP2 Inhibitors

Abstract

The present invention provides a compound of formula I, their synthesis and their use for treating a SHP2 mediated disorder. More particularly, the present invention provides a pharmaceutical composition comprising the said compound.

What is claimed is: 
     
         1 . A compound of formula I or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
       Wherein,
 ring A is a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
 G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, —NR G —SO 2 —, 
 
       
         
           
           
               
               
           
         
       
       —C(R G ) 2 — or —SO 2 —NR G —;
 each of R G  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted or unsubstituted; 
 ring B is a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring, a 3-10 membered carbocyclic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
 T is absent, O, NR 1  or CR 1 R 2 ; 
 each of R 1  and R 2  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; or 
 R I  and R 2  together with the carbon atom to which they are both attached form CO or C═NR 5 ; 
 p is 0, 1, 2, 3 or 4; 
 each of R 3  and R 4  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; or 
 R 3  and R 4  together with the carbon atom to which they are both attached form a 3-12 membered heterocyclic ring or a 5-12 membered heteroaromatic ring or C═NR 5 , and each of the ring systems is independently optionally substituted or unsubstituted; 
 each of R 5  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy; 
 q is 0, 1, 2, 3 or 4; 
 W is absent, O, S or —C(R W ) 2 -; and each of R W  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-6 alkyl, —CO—OC 1-6 alkyl, —C 1-6 alkylene-O—C 1-6 alkoxy, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; 
 ring C is absent, a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
 when ring C is absent, Y 5  is CR 5a R 5b , NR 5a  or O, and Y 6  is CR 6a R 6b , NR 6a  or O; 
 when ring C is a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring;
 i) Y 5  is CR 5a  or N, and Y 6  is CR 6a  or N, when the “ ” in the term “Y 5   Y 6 ” represents a single bond; or 
 ii) Y 5  is C, and Y 6  is C, when the “ ” in the term “Y 5   Y 6 ” represents a double bond; 
 
 each of R 5a  and R 5b  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; 
 each of R 6a  and R 6b  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; 
 each of R a  is independently selected from hydrogen, deuterium, halogen, —NR a1 R a2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, —C 1-6 alkoxy, —C 1-6 alkyl, —C 3-8 cycloalkyl, —C 1-6 alkylene—NR a1 R a2 , —C 1-6 alkylene-O—C 1-6 alkyl, —C 1-6 alkylene-(3-10 membered heterocyclic), —C 1-6 alkylene-(5-10 membered heteroaryl), —C 1-6 alkylene—CO—NR a1 R a2 , —C 1-6 alkylene—NR a1 —CO—NR a1 R a2 , —C 1-6 alkylene—NR a1 —CO—C 1-6 alkyl, —CO—NR a1 R a2 , —CO—CO—NR a1 R a2 , —C 3-10 carbocyclic, −5-10 membered heteroaryl, −3-10 membered heterocyclic, —CO—C 1-6 alkyl, —CO—C 1-6 alkylene—NR a1 R a2 , —CO—NR a1 -(3-10 membered heterocyclic), —CO—NR a1 -(3-10 membered heterocyclic), —CO-(3-10 membered heterocyclic), —O—C 1-6 alkylene—CO—OR a1 , —O—C 1-6 alkylene—CO—NR a1 R a2 , —O—C 1-6 alkylene—NR a1 R a2 , —O—C 3-10 carbocyclic, —O-(3-10 membered heterocyclic), —NR a1 —CO—C 1-6 alkyl, —NR a1 —CO—NR a1 R a2 , —NR a1 —CO-(5-10 membered heteroaryl), —NR a1 —CO—C 3-8 cycloalkyl,—NR a1 —C 1-6 alkylene—NR a1 R a2 , —NR a1 —C 1-6 alkylene-(3-10 membered heterocyclic), —NR a1 —C 1-6 alkylene-(5-10 membered heteroaryl), —NR a1 —SO 2 C 1-6 alkyl, —S—C 1-6 alkyl, —SONR a1 R a2 , —SO 2 NR a1 R a2 , —SO—C 1-6 alkyl, —SO 2 —C 1-6 alkyl, —PO(C 1-6 alkyl) 2 , —PO(C 1-6 alkoxy) 2 ,−3-10 membered heterocyclic or −5-10 membered heteroaryl; each of which is independently optionally substituted; and n iso, 1, 2, 3, 4, 5 or 6; or 
 two adjacent R a  can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3-6 membered heterocyclic ring or a 3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted; or 
 R a  and R w  with the atom to which they are both attached form a 3-10 membered aromatic ring, a 3-10 membered heteroaromatic ring or a 3-10 membered heterocyclic ring; and each of the ring systems is independently optionally substituted; 
 each of R a1  and R a2  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
 
     
     
         2 . The compound or pharmaceutically acceptable salt thereof of  claim 1 , wherein ring A is a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         3 . The compound or pharmaceutically acceptable salt thereof of  claim 1  or  claim 2 , wherein ring A is a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         4 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 3 , wherein ring A is a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         5 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 4 , wherein ring A is 
       
         
           
           
               
               
           
         
           represents a single bond or a double bond; 
         X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; 
         each of R X1  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; 
         X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; 
         each of R X2  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —CO—C 1-6 alkyl, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —SF 5 , —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene—C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or 
         R X1  and R X2  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
         X 3  is N, S, O, NR X3 , C(R X3 ) 2  or CR X3 ; 
         each of R X3  is independently selected from hydrogen, deuterium, halogen, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl, —C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl, —O—C 1-6 alkylene-C 1-6 alkoxy, —O—C 5-8 aryl or —O—C 1-6 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or 
         R X2  and R X3  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted ; 
         X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; 
         each of R X4  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl, —C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or a 5-12 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or 
         R X3  and R X4  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
         X 5  is N, S, NR X5 , C(R X5 ) 2  or CR X5 ; 
         each of R X5  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or 
         R X4  and R X5  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
         X 6  is O, S, CO or NR X6 , or C(R X6 ) 2 ; 
         each of R X6  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or 
         R X5  and R X6  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted. 
       
     
     
         6 . The compound or pharmaceutically acceptable salt thereof of  claim 5 , wherein X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         7 . The compound or pharmaceutically acceptable salt thereof of  claim 5  or  claim 6 , wherein X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         8 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 7 , wherein X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         9 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 8 , wherein X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         10 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 9 , wherein X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         11 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 10 , wherein X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; each of R X2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —CO—C 1-6 alkyl, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —SF 5 , —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene-C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         12 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 11 , wherein X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; each of R X2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —CO—C 1-6 alkyl, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —SF 5 , —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene-C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         13 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 12 , wherein X 2  is N, S, NR X2 , C(R X2 ) 2 ,CR X2  or CO; each of R X2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-4 alkyl, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene-C 3-6 cycloalkyl or 3-6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         14 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 13 , wherein X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; each of R X2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, methoxy, ethoxy, propoxy, isopropoxy, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene-C 3-6 cycloalkyl, 3 membered heterocyclic, 4 membered heterocyclic, 5 membered heterocyclic or 6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         15 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 14 , wherein X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; each of R X2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, methoxy, ethoxy, propoxy, isopropoxy, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene—C 3-6 cycloalkyl, 3 membered heterocyclic, 4 membered heterocyclic, 5 membered heterocyclic or 6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         16 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 15 , wherein R X1  and R X2  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         17 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 16 , wherein R X1  and R X2  together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         18 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 17 , wherein R X1  and R X2  together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N or O, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         19 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 18 , wherein X 3  is N, S, O, NR X3 , C(R X3 ) 2  or CR X3 ; each of R X3  is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl, —C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl, —O—C 1-6 alkylene-C 1-6 alkoxy, —O—C 5-8 aryl or —O—C 1-6 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         20 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 19 , wherein X 3  is N, S, O, NR X3 , C(R X3 ) 2  or CR X3 ; each of R X3  is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl, —C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl,—O—C 1-6 alkylene-C 1-6 alkyl, —O—C 5-8 aryl or —O—C 1-6 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         21 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 20 , wherein X 3  is N, S, O, NR X3 , C(R X3 ) 2  or CR X3 ; each of R X3  is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-3 alkyl, —C 1-3 alkoxy, C 3-6 cycloalkyl, C 5-8 aryl, —S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl, —O—C 1-3 alkylene-C 1-3 alkyl, —O—C 5-6 aryl or —O—C 1-3 alkylene-C 5-6 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         22 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 21 , wherein X 3  is N, S, O, NR X3 , C(R X3 ) 2  or CR X3;  each of R X3  is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, C 3-6 cycloalkyl, C 5-8 aryl, —S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl, —O—C 1-3 alkylene-C 1-3 alkyl, —O—C 5-6 aryl or —O—C 1-3 alkylene-C 5-6 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         23 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 22 , wherein X 3  is N, S, O, NR X3 , C(R X3 ) 2  or CR X3 ; each of R X3  is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, C 3-6 cycloalkyl, C 5-8 aryl, -S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl, —O—C 1-3 alkylene—C 1-3 alkyl, —O—C 5-6 aryl or —O—C 1-3 alkylene-C 5-6 aryl, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         24 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 23 , wherein R X2  and R X3  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         25 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 24 , wherein R X2  and R X3  together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         26 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 25 , wherein R X2  and R X3  together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, an 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N or O, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         27 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 26 , wherein X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; each of R X4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl, —C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or 5-12 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         28 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 27 , wherein X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; each of R X4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl, —C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or 5-12 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         29 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 28 , wherein X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; each of R X4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-3 alkyl, —C 1-3 alkoxy, —NHCO-(5-10 membered heterocyclyl) or 5-10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         30 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 29 , wherein X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; each of R X4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NHCO-(5-10 membered heterocyclyl), 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl or 10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         31 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 30 , wherein X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; each of R X4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NHCO-(5-10 membered heterocyclyl), 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl or 10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         32 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 31 , wherein R X3  and R X4  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         33 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 32 , wherein R X3  and R X4  together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         34 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 33 , wherein R X3  and R X4  together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         35 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 34 , wherein X 5  is N, S, NR X5 , C(R X5 ) 2  or CR X5 ; each of R X5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         36 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 35 , wherein X 5  is N, S, NR X5 , C(R X5 ) 2  or CR X5 ; each of R X5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or -C 1-3 alkoxy. 
     
     
         37 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 36 , wherein X 5  is N, S, NR X5 , C(R X5 ) 2  or CR X5 ; each of R X5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         38 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 37 , wherein X 5  is N, S, NR X5 , C(R X5 ) 2  or CR X5 ; each of R X5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         39 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 38 , wherein X 5  is N, S, NR X5 , C(R X5 ) 2  or CR X5 ; each of R X5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         40 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 39 , wherein R X4  and R X5 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         41 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 40 , wherein R X4  and R X5 together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         42 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 41 , wherein R X4  and R X5  together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         43 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 42 , wherein X 6  is O, S, CO or NR X6 , or C(R X6 ) 2 ; each of R X6  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         44 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 43 , wherein X 6  is O, S, CO or NR X6,  or C(R X6 ) 2 ; each of R X6  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         45 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 44 , wherein X 6  is O, S, CO or NR X6,  or C(R X6 ) 2 ; each of R X6  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         46 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 45 , wherein X 6  is O, S, CO or NR X6 , or C(R X6 ) 2 ; each of R X6  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         47 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 46 , wherein X 6  is O, S, CO or NR X6 , or C(R X6 ) 2 ; each of R X6  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         48 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 47 , wherein R X5  and R X6  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         49 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 48 , wherein R X5  and R X6  together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         50 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 49 , wherein R X5  and R X6  together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         51 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 5 - 50 , wherein ring A is selected from 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         52 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 51 , 
       wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, —NR G —SO 2 —, 
       
         
           
           
               
               
           
         
       
       —C(R G ) 2 — or —SO 2 —NR G —; each of R G  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted or unsubstituted. 
     
     
         53 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 52 , wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, —NR G —SO 2 —, 
       
         
           
           
               
               
           
         
       
       —C(R G ) 2 — or —SO 2 —NR G —; each of R G  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted or unsubstituted. 
     
     
         54 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 53 , wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, —NR G —SO 2 —, 
       
         
           
           
               
               
           
         
       
       —C(R G ) 2 — or —SO 2 —NR G —; each of R G  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted or unsubstituted. 
     
     
         55 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 54 , wherein ring B is a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring, a 3-10 membered carbocyclic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2,3, 4, 5 or 6 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2, 3, 4, 5 or 6heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         56 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 55 , wherein ring B is a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring, a 3-10 membered carbocyclic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2,3, 4, 5 or 6 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         57 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 56 , wherein ring B is a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered carbocyclic ring, a 6 membered carbocyclic ring, a 7 membered carbocyclic ring, a 8 membered carbocyclic ring, a 9 membered carbocyclic ring, a 10 membered carbocyclic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, a 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2, 3 or 4 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2, 3 or 4 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         58 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 57 , 
       wherein ring B is 
       
         
           
           
               
               
           
         
         Y 1  is N or CR Y1 , 
         R Y1  is selected from hydrogen, deuterium, halogen, —NH 2 , —OH, —CN, —N—(C 1-6 alkyl) 2 , —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; 
         Y 2  is N or CR Y2 ; 
         R Y2  is selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —N—(C 1-6 alkyl) 2 , alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or 
         R Y1 and R Y2 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
         when the “ ” in the term “Y 3   Y 4 ” represents a single bond, Y 3  is NR Y3  or C(R Y3 ) 2 , and Y 4  is CO, C(R Y4 ) 2  or NR Y4 ; 
         when the “ ” in the term “Y 3   Y 4 ” represents a double bond, Y 3  is N or CR Y3 , and Y 4  is N or CR Y4 ; 
         R Y3  and R Y4  are independently selected from hydrogen, deuterium, halogen, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH —CO—C 3-8 heterocyclic ring, —CONH 2  or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl, —C 1-6 alkyl substituted with —OH, or —C 1-6 alkoxy; or 
         R Y3  and R Y4 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted. 
       
     
     
         59 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 58 , wherein Y 1  is N or CR Y1 ; R Y1  is selected from hydrogen, deuterium, F, Cl, Br, I, —NH 2 , —OH, —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         60 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 59 , wherein Y 1  is N or CR Y1 ; R Y1  is selected from hydrogen, deuterium, F, Cl, Br, I, —NH 2 , —OH, —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         61 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 60 , wherein Y 1  is N or CR Y1 ; R Y1  is selected from hydrogen, deuterium, F, Cl, Br, I, —NH 2 , —OH, —CN, —C 1-3 alkyl, —C 1-3 alkoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         62 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 61 , wherein Y 1  is N or CR Y1 ; R Y1  is selected from hydrogen, deuterium, F, Cl, Br, I, —NH 2 , —OH, —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         63 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 62 , wherein Y 2  is N or CR Y2 ; R Y2  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6  alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         64 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 63 , wherein Y 2  is N or CR Y2 ; R Y2  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6  alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         65 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 64 , wherein Y 2  is N or CR Y2 ; R Y2  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl, —C 1-3 alkoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         66 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 65 , wherein Y 2  is N or CR Y2 ; Rye is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         67 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 66 , wherein R Y1  and R Y2  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         68 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 67 , wherein R Y1  and R Y2  together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         69 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 68 , wherein R Y1 and R Y2 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         70 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 69 , wherein R Y3  and R Y4  are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH, —C 1-6 alkylene—OH, —CO—C 3-8 heterocyclic ring, —CONH 2  or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl, —C 1-6 alkyl substituted with —OH or —C 1-6 alkoxy. 
     
     
         71 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 70 , wherein R Y3  and R Y4  are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH, —C 1-6 alkylene—OH, —CO—C 3-8 heterocyclic ring, —CONH 2  or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl, —C 1-3 alkyl substituted with —OH or —C 1-3 alkoxy. 
     
     
         72 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 71 , wherein R Y3  and R Y4  are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-3 alkyl, carboxyl, —COO—C 1-3 alkyl, —NH—C 1-3 alkylene—OH, —C 1-3 alkylene—OH, —CO—C 3-8 heterocyclic ring, —CONH 2  or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl, —C 1-3 alkyl substituted with —OH or —C 1-3 alkoxy. 
     
     
         73 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 72 , wherein R Y3  and R Y4  are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, methyl, ethyl, propyl, isopropyl, carboxyl, —COO—C 1-3 alkyl, —NH—C 1-3 alkylene—OH, —C 1-3 alkylene—OH, —CO—C 3-8 heterocyclic ring, —CONH 2  or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, ethyl substituted with —OH, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         74 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 73 , wherein R Y3  and R Y4 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         75 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 74 , wherein R Y3  and R Y4  together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         76 . The compound or pharmaceutically acceptable salt there of any one of  claims 1 - 75 , wherein R Y3  and R Y4 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         77 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 75 , wherein ring B is selected from 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         78 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 77 , wherein each of R 1  and R 2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
     
     
         79 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 78 , wherein each of R 1  and R 2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-3 alkyl, —N(C 1-3 alkyl) 2 , substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl. 
     
     
         80 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 79 , wherein each of R 1  and R 2  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         81 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 80 , wherein each of R 1  and R 2  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         82 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 81 , wherein R 1  and R 2  together with the carbon atom to which they are both attached form CO or C═NR 5.    
     
     
         83 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 82 , wherein R 1  and R 2  together with the carbon atom to which they are both attached form CO. 
     
     
         84 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 83 , wherein R 1  and R 2  together with the carbon atom to which they are both attached form C═NR 5.    
     
     
         85 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 84 , wherein each of R 3  and R 4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
     
     
         86 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 85 , wherein each of R 3  and R 4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-3 alkyl, —N(C 1-3 alkyl) 2 , substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl. 
     
     
         87 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 86 , wherein each of R 3  and R 4  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         88 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 87 , wherein each of R 3  and R 4  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         89 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 88 , wherein R 3  and R 4  together with the carbon atom to which they are both attached form 3-12 membered heterocyclic ring or 5-12 membered heteroaromatic ring or C═NR 5 ; and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         90 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 89 , wherein R 3  and R 4  together with the carbon atom to which they are both attached form 3-10 membered heterocyclic ring or 5-10 membered heteroaromatic ring or C═NR 5 ; and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         91 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 90 , wherein R 3  and R 4  together with the carbon atom to which they are both attached form 3 membered heterocyclic ring, 4 membered heterocyclic ring, 5 membered heterocyclic ring, 6 membered heterocyclic ring, 7 membered heterocyclic ring, 8 membered heterocyclic ring, 9 membered heterocyclic ring, 10 membered heterocyclic ring, 5 membered heteroaromatic ring, 6 membered heteroaromatic ring, 7 membered heteroaromatic ring, 8 membered heteroaromatic ring, 9 membered heteroaromatic ring, 10 membered heteroaromatic ring or C═NR 5 ; and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         92 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 91 , wherein each of R 5  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         93 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 92 , wherein each of R 5  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         94 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 93 , wherein each of R 5  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy 
     
     
         95 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 94 , wherein W is absent, —O, —S or —C(R W ) 2 -; and each of R W  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-6 alkyl, —CO—OC 1-6 alkyl, —C 1-6 alkylene-O—C 1-6 alkoxy, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
     
     
         96 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 95 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-3 alkyl, —CO—OC 1-3 alkyl, —C 1-3 alkylene-O—C 1-3 alkoxy, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl. 
     
     
         97 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 96 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkylene-O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         98 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 97 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkylene-O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         99 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 98 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkylene-O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         100 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 99 , wherein ring C is absent, a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         101 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 100 , wherein ring C is absent, a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         102 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 101 , wherein ring C is absent, a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         103 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 102 , wherein ring C is selected from 
       
         
           
           
               
               
           
         
       
     
     
         104 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 103 , wherein each of R 5a  and R 5b  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
     
     
         105 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 104 , wherein each of R 5a  and R 5b  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl. 
     
     
         106 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 105 , wherein each of R 5a  and R 5b  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         107 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 106 , wherein each of R 5a  and R 5b  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         108 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 107 , wherein each of RY 6 , and R 6b  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
     
     
         109 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 108 , wherein each of R 6a  and R 6b  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl. 
     
     
         110 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 109 , wherein each of R 6a  and R 6b  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         111 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 110 , wherein each of Rha and R 6b  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         112 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 111 , wherein each of R a  is independently hydrogen, deuterium, F, Cl, Br, —NR a1 R a2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, —C 1-3 alkoxy,—C 1-4 alkyl, —C 3-6 cycloalkyl, —C 1-3 alkylene—NR a1 R a2 , —C 1-3 alkylene-O—C 1-6 alkyl, —C 1-3 alkylene-(3-8 membered heterocyclic), —C 1-3 alkylene-(5-8 membered heteroaryl), —C 1-3 alkylene—CO—NR a1 R a2 , —C 1-3 alkylene—NR a1 —CO—NR a1 R a2 , —C 1-3 alkylene—NR a1 —CO—C 1-3 alkyl, —CO—NR a1 R a2 , —CO—CO—NR a1 R a2 , —C 3-8 carbocyclic, −5-8 membered heteroaryl, −3-8 membered heterocyclic, —CO—C 1-3 alkyl, —COO—C 1-3 alkyl, —CO—C 1-3 alkylene—NR a1 R a2 , —CO—NR-(3-8 membered heterocyclic), —CO—NR-(3-8 membered heterocyclic), —CO-(3-8 membered heterocyclic), —O—C 1-3 alkylene—CO—OR a1 , —O—C 1-3 alkylene—CO—NR a1 R a2 , —O—C 1-3 alkylene—NR a1 R a2 , —O—C 3-8 carbocyclic, —O-(3-8 membered heterocyclic), —NR a1 —CO—C 1-3 alkyl, —NR a1 —CO—NR a1 R a2 , —NR a1 —CO-(5-8 membered heteroaryl), —NR a1 —CO—C 3-6 cycloalkyl,—NR a1 —C 1-3 alkylene—NR a1 R a2 , —NR a1 —C 1-3 alkylene-(3-8 membered heterocyclic), —NR a1 —C 1-3 alkylene-(5-8 membered heteroaryl), —NR a1 —SO 2 C 1-3 alkyl, —S—C 1-3 alkyl, —SONR a1 R a2 , —SO 2 NR a1 R a2 , —SO—C 1-3 alkyl, —SO 2 —C 1-3 alkyl, —PO(C 1-3 alkyl) 2 , —PO(C 1-3 alkoxy) 2 , −3-8 membered heterocyclic or −5-8 membered heteroaryl; each of which is independently optionally substituted; and n is 0, 1, 2, 3, 4, 5 or 6. 
     
     
         113 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 112 , wherein each of R a  is independently hydrogen, deuterium, F, Cl, Br, —NR a1 R a2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, methoxy, ethoxy, propoxy, isopropoxy methyl, ethyl, propyl, isopropyl, butyl, isobutyl, —C 3-6 cycloalkyl,-C 1-3 alkylene—NR a1 R a2 , —C 1-3 alkylene-O—C 1-6 alkyl, —C 1-3 alkylene—CO—OR a1 , —C 1-3 alkylene-(3-8 membered heterocyclic), —C 1-3 alkylene-(5-8 membered heteroaryl), —C 1-3 alkylene—CO—NR a1 R a2 , —C 1-3 alkylene—NR a1 —CO—NR a1 R a2 , —CO—NR a1 R a2 , —CO—CO—NR a1 R a2 , —C 3-8 carbocyclic, −5-8 membered heteroaryl, −3-8 membered heterocyclic, —CO—C 1-3 alkyl, —COO—C 1-3 alkyl, —CO—C 1-3 alkylene—NR a1 R a2 , —CO—NR-(3-8 membered heterocyclic), —CO—NR-(3-8 membered heterocyclic), —CO-(3-8 membered heterocyclic), —O—C 1-3 alkylene—CO—OR a1 , —O—C 1-3 alkylene—CO—NR a1 R a2 , —O—C 1-3 alkylene-NR a1 R a2 , —O—C 3-8 carbocyclic, —O-(3-8 membered heterocyclic), —NR a1 —CO—C 1-3 alkyl, -NL1—CO—NR a1 R a2 , -NL1—CO-(5-8 membered heteroaryl), -NLI—CO—C 3-6 cycloalkyl,—NR a1 —C 1-3 alkylene—NR a1 R a2 , —NR a1 —C 1-3 alkylene-(3-8 membered heterocyclic), —NR a1 —C 1-3 alkylene-(5-8 membered heteroaryl), —NR a1 —SO 2 C 1-3 alkyl, —S—C 1-3 alkyl, —SONR a1 R a2 , —SO 2 NR a1 R a2 , —SO—C 1-3 alkyl, −50 2 —C 1-3 alkyl, —PO(C 1-3 alkyl) 2 , —PO(C 1-3 alkoxy) 2 , −3-8 membered heterocyclic or −5-8 membered heteroaryl; each of which is independently optionally substituted; and n is 0, 1, 2, 3, 4, 5 or 6. 
     
     
         114 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 113 , wherein two adjacent R a  can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3-6 membered heterocyclic ring or a 3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted with deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         115 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 114 , wherein two adjacent R a  can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3-6 membered heterocyclic ring or a 3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         116 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 115 , wherein two adjacent R a  can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3 membered heterocyclic ring, a 4 membered heterocyclic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 3 membered carbocyclic ring, a 4 membered carbocyclic ring, a 5 membered carbocyclic ring, a 6 membered carbocyclic ring, wherein each of the heteroaryl contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         117 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 116 , R a  and R w  with the atom to which they are both attached form a 3-10 membered aromatic ring, a 3-10 membered heteroaromatic ring or a 3-10 membered heterocyclic ring; and each of the ring systems is independently optionally substituted with deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         118 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 117 , R a  and R w  with the atom to which they are both attached form a 3-10 membered aromatic ring, a 3-10 membered heteroaromatic ring or a 3-10 membered heterocyclic ring; and each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, -C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         119 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 118 , R a  and R w  with the atom to which they are both attached form a 3-10 membered aromatic ring, a 3-10 membered heteroaromatic ring or a 3-10 membered heterocyclic ring; each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S; each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S; and each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         120 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 116 , R a  and R w  with the atom to which they are both attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 5 membered heteroaryl ring, a 6 membered heteroaryl ring, a 5 membered heterocyclic ring or a 6 membered heterocyclic ring; each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S; each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S; and each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         121 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 120 , wherein each of R a1 and R a2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted -C 1-6 alkyl. 
     
     
         122 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 121 , wherein each of R a1 and R a2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl. 
     
     
         123 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 122 , wherein each of R a1 and R a2  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         124 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 123 , wherein each of R a1 and R a2  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         125 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 124 , wherein the compound is of Formula II: 
       
         
           
           
               
               
           
         
         X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; 
         each of R X1  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; 
         X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; 
         each of R X2  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —CO—C 1-6 alkyl, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —SF S , —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene—C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or 
         R X1  and R X2  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
         X 3  is N, S, NR X3 , C(R X3 ) 2  or CR X3 ; 
         each of R X3  is independently selected from hydrogen, deuterium, halogen, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl, —C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl, —O—C 1-6 alkylene-C 1-6 alkoxy, —O—C 5-8 aryl or —O—C 1-6 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or 
         R X2  and R X3  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted ; 
         X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; 
         each of R X4  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl,-C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or 5-12 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or 
         R X3  and R X4  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
         X 5  is N, S, NR X5 , C(R X5 ) 2  or CR X5 ; 
         each of R X5  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or 
         R X4  and R X5  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
           represents a single bond or a double bond; 
         G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, —NR G —SO 2 —, 
       
       
         
           
           
               
               
           
         
       
       —C(R G ) 2 — or —SO 2 —NR G —;
 each of R G  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted or unsubstituted; 
 Y 1  is N or CR Y1 , 
 R Y1  is selected from hydrogen, deuterium, halogen, —NH 2 , —OH, —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; 
 Y 2  is N or CR Y2 ; 
 R Y2  is selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6  alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or 
 R Y1  and R Y2  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
 when the “ ” in the term “Y 3   Y 4 ” represents a single bond, Y 3  is NR Y3  or C(R Y3 ) 2 , and Y 4  is CO, C(R Y4 ) 2  or NR Y4 ; 
 when the “ ” in the term “Y 3   Y 4 ” represents a double bond, Y 3  is N or CR Y3 , and Y 4  is N or CR Y4 ; 
 R Y3  and R Y4  are independently selected from hydrogen, deuterium, halogen, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH , —C 1-6 alkylene—OH, —CONH 2  or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or 
 R Y3  and R Y4 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
 T is absent, O, NR 1  or CR 1 R 2 ; 
 each of R 1  and R 2  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; or 
 R 1  and R 2  together with the carbon atom to which they are both attached form CO or C═NR 5 ; 
 p is 0, 1, 2 or 3; 
 each of R 3  and R 4  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; or 
 R 3  and R 4  together with the carbon atom to which they are both attached form a 3-12 membered heterocyclic ring or a 5-12 membered heteroaromatic ring or C═NR 5 , and each of the ring systems is independently optionally substituted or unsubstituted; 
 each of R 5  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy; 
 q is 0, 1, 2, 3 or 4; 
 W is absent, —O, —S or —C(R W ) 2 —; and each of R W  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-6 alkyl, —CO—OC 1-6 alkyl, C 1-6 alkoxy, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; 
 ring C is absent, a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
 when ring C is absent, Y 5  is CR 5a R 5b , NR 5a  or O, and Y 6  is CR 6a R 6b , NR 6a  or O; 
 when ring C is a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring;
 i) Y 5  is CR 5a  or N, and Y 6  is CR 6a  or N, when the “ ” in the term “Y 5   Y 6 ” represents a single bond; or 
 ii) Y 5  is C, and Y 6  is C, when the “ ” in the term “Y 5   Y 6 ” represents a double bond; 
 
 each of R 5a  and R 5b  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; 
 each of R 6a  and R 6b  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; 
 each of R a  is independently hydrogen, deuterium, halogen, —NR a1 R a2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, —C 1-6 alkoxy, —C 1-6 alkyl, —C 3-8 cycloalkyl,-C 1-6 alkylene—NR a1 R a2 , —C 1-6 alkylene-O—C 1-6 alkyl, —C 1-6 alkylene-(3-10 membered heterocyclic), —C 1-6 alkylene-(5-10 membered heteroaryl), —C 1-6 alkylene—CO—NR a1 R a2 , —C 1-6 alkylene—NR a1 —CO—NR a1 R a2 , —C 1 , 6 alkylene—NR a1 —CO—C 1-6 alkyl, —CO—NR a1 R a2 , —CO—CO—NR a1 R a2 , —C 3-10 carbocyclic, −5-10 membered heteroaryl, −3-10 membered heterocyclic, —CO—C 1-6 alkyl, —CO—C 1-6 alkylene—NR a1 R a2 , —CO—NR a1 -(3-10 membered heterocyclic), —CO—NR a1 -(3-10 membered heterocyclic), —CO-(3-10 membered heterocyclic), —O—C 1-6 alkylene—CO—OR a1 , —O—C 1-6 alkylene—CO—NR a1 R a2 , —O—C 1-6 alkylene—NR a1 R a2 , —O—C 3-10 carbocyclic, —O-(3-10 membered heterocyclic), —NR a1 —CO—C 1-6 alkyl, —NR a1 —CO—NR a1 R a2 , —NR a1 —CO-(5-10 membered heteroaryl), —NR a1 —CO—C 3-8 cycloalkyl,—NR a1 —C 1-6 alkylene—NR a1 R a2 , —NR a1 —C 1-6 alkylene-(3-10 membered heterocyclic), —NR a1 —C 1-6 alkylene-(5-10 membered heteroaryl), —NR a1 —SO 2 C 1-6 alkyl, —S—C 1-6 alkyl, —SONR a1 R a2 , —SO 2 NR a1 R a2 , —SO—C 1-6 alkyl, —PO(C 1-6 alkyl) 2 , —PO(C 1-6 alkoxy) 2 , −3-10 membered heterocyclic or −5-10 membered heteroaryl; each of which is independently optionally substituted; and n is 0, 1, 2, 3, 4, 5 or 6; or 
 two adjacent R a  can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3-6 membered heterocyclic ring or a 3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted; 
 each of R a1  and R a2  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
 
     
     
         126 . The compound or pharmaceutically acceptable salt thereof of  claim 125 , wherein X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         127 . The compound or pharmaceutically acceptable salt thereof of  claim 122  or  claim 126 , wherein X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         128 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 127 , wherein X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         129 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 128 , wherein X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         130 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 129 , wherein X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         131 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 130 , wherein X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; each of R X2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —CO—C 1-6 alkyl, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —SFS, —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene-C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         132 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 131 , wherein X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; each of R X2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —CO—C 1-6 alkyl, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —SF 5 , —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene-C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         133 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 132 , wherein X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; each of R X2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl, —C 1-3 alkoxy, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene—C 3-6 cycloalkyl or 3-6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         134 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 133 , wherein X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; each of R X2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene-C 3-6 cycloalkyl, 3 membered heterocyclic, 4 membered heterocyclic, 5 membered heterocyclic or 6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         135 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 134 , wherein X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; each of R X2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene-C 3-6 cycloalkyl, 3 membered heterocyclic, 4 membered heterocyclic, 5 membered heterocyclic or 6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         136 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 135 , wherein R X1  and R X2  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         137 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 137 , wherein R X1  and R X2  together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         138 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 137 , wherein R X1  and R X2  together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N or O, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         139 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 138 , wherein X 3  is N, S, NR X3 , C(R X3 ) 2  or CR X3;  each of R X3  is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl, —C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl,—O—C 1-6 alkylene-C 1-6 alkoxy, —O—C 5-8 aryl or —O—C 1-6 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         140 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 139 , wherein X 3  is N, S, NR X3 , C(R X3 ) 2  or CR X3 ; each of R X3  is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl, —C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl, —O—C 1-6 alkylene-C 1-6 alkoxy, —O—C 5-8 aryl or —O—C 1-6 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         141 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 140 , wherein X 3  is N, S, NR X3 , C(R X3 ) 2  or CR X3 ; each of R X3  is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-3 alkyl, —C 1-3 alkoxy, C 3-6 cycloalkyl, C 5-8 aryl, —S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl, —O—C 1-3 alkylene-C 1-3 alkoxy, —O—C 5-8 aryl or —O—C 1-6 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         142 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 141 , wherein X 3  is N, S, NR X3 , C(R X3 ) 2  or CR X3 ; each of R X3  is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, C 3-6 cycloalkyl, C 5-8 aryl, -S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl or —O—C 1-3 alkylene—C 1-3 alkoxy, −0—C 5-8 aryl or —O—C 1-3 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         143 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 142 , wherein X 3  is N, S, NR X3 , C(R X3 ) 2  or CR X3 ; each of R X3  is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, C 3-6 cycloalkyl, C 5-8 aryl, -S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl or —O—C 1-3 alkylene-C 1-3 alkoxy, —O—C 5-8 aryl or —O—C 1-3 alkylene-C 5-8 aryl, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         144 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 143 , wherein R X2  and R X3  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         145 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 144 , wherein R X2  and R X3  together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         146 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 145 , wherein R X2  and R X3  together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N or O, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         147 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 146 , wherein X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; each of R X4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl, —C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or 5-12 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         148 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 147 , wherein X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; each of R X4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl, —C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or 5-12 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         149 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 148 , wherein X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; each of R X4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-3 alkyl, —C 1-3 alkoxy, —NHCO-(5-10 membered heterocyclyl) or 5-10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         150 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 149 , wherein X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; each of R X4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NHCO-(5-10 membered heterocyclyl), 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl or 10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         151 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 150 , wherein X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; each of R X4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NHCO-(5-10 membered heterocyclyl), 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl or 10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         152 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 151 , wherein R X3  and R X4  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         153 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 152 , wherein R X3  and R X4  together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         154 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 153 , wherein R X3  and R X4  together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         155 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 154 , wherein X 5  is N, S, NR X5 , C(R X5 ) 2  or CR X5 ; each of R X5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         156 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 155 , wherein X 5  is N, S, NR X5 , C(R X5 ) 2  or CR X5 ; each of R X5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         157 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 156 , wherein X 5  is N, S, NR X5 , C(R X5 ) 2  or CR X5 ; each of R X5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         158 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 157 , wherein X 5  is N, S, NR X5 , C(R X5 ) 2  or CR X5 ; each of R X5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         159 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 158 , wherein X 5  is N, S, NR X5 , C(R X5 ) 2  or CR X5 ; each of R X5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         160 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 159 , wherein R X4  and R X5  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         161 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 160 , wherein R X4  and R X5  together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         162 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 161 , wherein R X4  and R X5  together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         163 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 162 , wherein ring A is selected from 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         164 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 163 , wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, 
       
         
           
           
               
               
           
         
       
       —NR G —SO 2 —, —C(R G ) 2 — or —SO 2 —NR G —; each of R G  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted or unsubstituted. 
     
     
         165 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 164 , wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, —NR G —SO 2 —, 
       
         
           
           
               
               
           
         
       
       —C(R G ) 2 — or —SO 2 —NR G —; each of R G  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted or unsubstituted. 
     
     
         166 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 165 , wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, —NR G —SO 2 —, 
       
         
           
           
               
               
           
         
       
       —C(R G ) 2 — or —SO 2 —NR G —; each of R G  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted or unsubstituted. 
     
     
         167 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 166 , wherein Y 1  is N or CR Y1 ; R Y1  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C s-m aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         168 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 167 , wherein Y 1  is N or CR Y1 ; R Y1  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         169 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 168 , wherein Y 1  is N or CR Y1 ; R Y1  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-3 alkyl, —C 1-3 alkoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         170 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 169 , wherein Y 1  is N or CR Y1 ; R Y1  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         171 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 170 , wherein Y 2  is N or CR Y2 ; R Y2  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6  alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         172 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 171 , wherein Y 2  is N or CR Y2 ; R Y2  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6  alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         173 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 172 , wherein Y 2  is N or CR Y2 ; R Y2  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl, —C 1-3 alkoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         174 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 173 , wherein Y 2  is N or CR Y2 ; R Y2  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         175 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 174 , R Y1  and R Y2  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         176 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 122 - 172 , R Y1  and R Y2  together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         177 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 176 , R Y1  and R Y2  together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         178 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 177 , wherein R Y3  and R Y4  are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH, —C 1-6 alkylene—OH, —CONH 2  or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         179 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 178 , wherein R Y3  and R Y4  are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH, —C 1-6 alkylene—OH, —CONH 2  or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         180 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 179 , wherein R Y3  and R Y4  are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-3 alkyl, carboxyl, —COO—C 1-3 alkyl, —NH—C 1-3 alkylene—OH, —C 1-3 alkylene—OH, —CONH 2  or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         181 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 180 , wherein R Y3  and R Y4  are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, methyl, ethyl, propyl, isopropyl, carboxyl, —COO—C 1-3 alkyl, —NH—C 1-3 alkylene—OH, —C 1-3 alkylene—OH, —CONH 2  or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         182 . The compound or pharmaceutically acceptable salt thereof of any one  claims 125 - 181 , wherein R Y3  and R Y4 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         183 . The compound or pharmaceutically acceptable salt thereof of any one  claims 125 - 182 , wherein R Y3  and R Y4  together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         184 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 183 , wherein R Y3  and R Y4 together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         185 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 184 , wherein ring B is selected from 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         186 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 185 , wherein each of R 1  and R 2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
     
     
         187 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 186 , wherein each of R 1  and R 2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-3 alkyl, —N(C 1-3 alkyl) 2 , substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl. 
     
     
         188 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 187 , wherein each of R 1  and R 2  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         189 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 188 , wherein each of R 1  and R 2  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         190 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 189 , wherein R 1  and R 2  together with the carbon atom to which they are both attached form CO or C═NR 5 . 
     
     
         191 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 190 , wherein R 1  and R 2  together with the carbon atom to which they are both attached form CO. 
     
     
         192 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 191 , wherein R 1  and R 2  together with the carbon atom to which they are both attached form C═NR 5 . 
     
     
         193 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 192 , wherein each of R 3  and R 4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
     
     
         194 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 193 , wherein each of R 3  and R 4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-3 alkyl, —N(C 1-3 alkyl) 2 , substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl. 
     
     
         195 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 194 , wherein each of R 3  and R 4  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         196 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 195 , wherein each of R 3  and R 4  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         197 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 196 , wherein R 3  and R 4  together with the carbon atom to which they are both attached form a 3-12 membered heterocyclic ring or a 5-12 membered heteroaromatic ring or C═NR 5 ; and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         198 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 197 , wherein R 3  and R 4  together with the carbon atom to which they are both attached form a 3-10 membered heterocyclic ring or a 5-10 membered heteroaromatic ring or C═NR 5 ; and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         199 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 198 , wherein R 3  and R 4  together with the carbon atom to which they are both attached form a 3 membered heterocyclic ring, a 4 membered heterocyclic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, a 10 membered heterocyclic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring or C═NR 5 ; and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         200 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 199 , wherein each of R 5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         201 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 200 , wherein each of R 5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         202 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 201 , wherein each of R 5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy 
     
     
         203 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 202 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-6 alkyl, —CO—OC 1-6 alkyl, —C 1-6 alkyl-O—C 1-6 alkoxy, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
     
     
         204 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 203 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-3 alkyl, —CO—OC 1-3 alkyl, —C 1-3 alkyl—O—C 1-3 alkoxy, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl. 
     
     
         205 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 204 , wherein W is absent, —O, —S or —C(R W ) 2 -; and each of R W  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkyl—O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         206 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 205 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkyl—O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         207 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 206 , wherein W is absent, —O, —S or —C(R W ) 2 -; and each of R W  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkyl—O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         208 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 207 , wherein ring C is absent, a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         209 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 208 , wherein ring C is absent, a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         210 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 209 , wherein ring C is absent, a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, a 8 membered heterocyclic ring, a 9 membered heterocyclic ring, a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         211 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 210 , wherein ring C is selected from 
       
         
           
           
               
               
           
         
       
     
     
         212 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 211 , wherein each of R 5a  and R 5b  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
     
     
         213 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 212 , wherein each of R 5a  and R 5b  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl. 
     
     
         214 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 213 , wherein each of R 5a  and R 5b  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         215 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 214 , wherein each of R sa  and R 5b  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         216 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 215 , wherein each of R 6a  and R 6b  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
     
     
         217 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 216 , wherein each of R 6a  and R 6b  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl. 
     
     
         218 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 217 , wherein each of R 6a  and R 6b  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         219 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 218 , wherein each of R 6a  and R 6b  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         220 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 219 , wherein each of R a  is independently selected from hydrogen, deuterium, F, Cl, Br, —NR a1 R a2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, —C 1-3 alkoxy, —C 1-3 alkyl, —C 3-6 cycloalkyl, —C 1-3 alkylene—NR a1 R a2 , —C 1-3 alkylene-O—C 1-6 alkyl, —C 1-3 alkylene—CO—OR a1 , —C 1-3 alkylene-(3-8 membered heterocyclic), —C 1-3 alkylene-(5-8 membered heteroaryl), —C 1-3 alkylene—CO—NR a1 R a2 , —C 1-3 alkylene-NR a1 —CO—C 1-3 alkyl, —CO—NR a1 R a2 , —CO—CO—NR a1 R a2 , —C 3-8 carbocyclic, −5-10 membered heteroaryl, −3-8 membered heterocyclic, —CO—C 1-3 alkyl, —COO—C 1-3 alkyl, —CO—C 1-3 alkylene-NR a1 R a2 , —CO—NR a1 -(3-8 membered heterocyclic), —CO—NR a1 -(3-8 membered heterocyclic), —CO-(3-8 membered heterocyclic), —O—C 1-3 alkylene-CO—OR a1 , —O—C 1-3 alkylene-CO—NR a1 R a2 , —O—C 1-3 alkylene-NR a1 R a2 , —O—C 3-8 carbocyclic, −0-(3-8 membered heterocyclic), —NR a1 —CO—C 1-3 alkyl, —NR a1 —CO—NR a1 R a2 , —NR a1 —CO-(5-8 membered heteroaryl), —NR a1 —CO—C 3-6 cycloalkyl, —NR a1 —C 1-3 alkylene—NR a1 R a2 , —NR a1 —C 1-3 alkylene-(3-8 membered heterocyclic), —NR a1 —C 1-3 alkylene-(5-8 membered heteroaryl), —NR a1 —SO 2  C 1 - 3 alkyl, —S—C 1-3 alkyl, —SO 2 NR a1 R a2 , —SO 2 NR a1 R a2 , —SO—C 1-3 alkyl, —SO 2 C 1-3 alkyl, —PO(C 1-3 alkyl) 2 , —PO(C 1-3 alkoxy) 2 , −3-8 membered heterocyclic or −5-8 membered heteroaryl; each of which is independently optionally substituted; and n is 0, 1, 2, 3, 4, 5 or 6. 
     
     
         221 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 220 , wherein each of R a  is independently selected from hydrogen, deuterium, F, Cl, Br, —NR a1 R a2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, methoxy, ethoxy, propoxy, isopropoxy methyl, ethyl, propyl, isopropyl, —C 3-6 cycloalkyl, —C 1-3 alkylene-NR a2 , —C 1-3 alkylene-O—C 1-6 alkyl, —C 1-3 alkylene-CO—OR a1 , —C 1-3 alkylene-(3-8 membered heterocyclic), —C 1-3 alkylene-(5-8 membered heteroaryl), —C 1-3 alkylene—NR a1 —C—NR a1 R a2 , —CO—NR a1 R a2 , —C 3-8 carbocyclic, −3-8 membered heterocyclic, —CO—C 1-3 alkyl, —COO—C 1-3 alkyl, —CO—C 1-3 alkylene-NR a1 R a2 , —CO—NR a1 -(3-8 membered heterocyclic), —CO-NR a1 -(3-8 membered heterocyclic), —CO-(3-8 membered heterocyclic), —O—C 1-3 alkylene-CO—OR a1 , —O—C 1-3 alkylene-CO—NR a1 R a2 , —O—C 1-3 alkylene-NR a1 R a2 , —O—C 3-8 carbocyclic, −O-(3-8 membered heterocyclic), —NR a1 —CO—C 1-3 alkyl, -NIU-00-(5-8 membered heteroaryl), —NR a1 —CO—C 3-6 cycloalkyl,—NR a1 —C 1-3 alkylene—NR a1 R a2 , —NR a1 —C 1-3 alkylene-(3-8 membered heterocyclic), —NR a1 —C 1-3 alkylene-(5-8 membered heteroaryl), —NR a1 —SO 2 C 1-3 alkyl, —S—C 1-3 alkyl, —SO 2 NR a1 R a2 , —SO—C 1-3 alkyl, —SO 2 C 1-3 alkyl, —PO(C 1-3 alkyl) 2 , —PO(C 1-3 alkoxy) 2 , −3-8 membered heterocyclic or −5-8 membered heteroaryl; each of which is independently optionally substituted; and n is 0, 1, 2, 3, 4, 5 or 6. 
     
     
         222 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 221 , wherein two adjacent R a  can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3-6 membered heterocyclic ring or a 3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted with deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         223 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 222 , wherein two adjacent R a  can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3-6 membered heterocyclic ring or a 3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         224 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 223 , wherein two adjacent R a  can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3 membered heterocyclic ring, a 4 membered heterocyclic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 3 membered carbocyclic ring, a 4 membered carbocyclic ring, a 5 membered carbocyclic ring, a 6 membered carbocyclic ring, wherein each of the heteroaryl contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         225 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 224 , wherein each of R a1  and R a2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted -C 1-6 alkyl. 
     
     
         226 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 225 , wherein each of R a1  and R a2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl. 
     
     
         227 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 226 , wherein each of R a1 and R a2  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ;
 —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; 
 —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
 
     
     
         228 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 227 , wherein each of R a1 and R a2  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ;
 —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
 
     
     
         229 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 228 , wherein the compound is of Formula II-a: 
       
         
           
           
               
               
           
         
         Wherein X 1 , X 2 , X 3 , X 4 , X 5 ; G, R Y1 , R Y3 , T, R 3 , R 4 , W, Y 5 ; Y 6 , R a , p, q and n are as defined in  claims 125 - 228 . 
       
     
     
         230 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 229 , wherein the compound is of Formula II-b 
       
         
           
           
               
               
           
         
         Wherein X 1 , X 2 , X 3 , X 4 , X 5 ; G, R Y1 , R Ya , T, R 3 , R 4 , W, Y 5 ; Y 6 , R a , p, q and n are as defined in  claims 125 - 228 . 
       
     
     
         231 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 125 - 230 , wherein the compound is of Formula II-c 
       
         
           
           
               
               
           
         
         Wherein X 1 , X 2 , X 3 , X 4 , X 5 ; G, R Y1 , R Y2 , R Ya , T, R 3 , R 4 , W, Y 5 ; Y 6 , R a , p, q and n are as defined in  claims 125 - 228 . 
       
     
     
         232 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 124 , wherein the compound is of Formula III: 
       
         
           
           
               
               
           
         
         X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; 
         each of R X1  is selected from hydrogen, deuterium, halogen, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxyl; 
         X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; 
         each of R X2  is selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —SF 5 , —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene—C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or 
         R X1  and R X2  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
         X 3  is N, S, O, NR X3 , C(R X3 ) 2  or CR X3 ; 
         each of R X3  is independently selected from hydrogen, deuterium, halogen, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl,-C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl or —O—C 1-6 alkylene-C 1-6 alkyl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or 
         R X2  and R X3  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted ; 
         X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; 
         each of R X4  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl, —C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or 5-12 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or 
         R X3  and R X4  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
         X 5  is N, NR X5  C(R X5 ) 2  or CR X5 ; 
         each of R X5  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; or 
         R X4  and R X5 together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
           represents a single bond or a double bond; 
         G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, —NR G —SO 2 —, 
       
       
         
           
           
               
               
           
         
       
       —C(R G ) 2 — or —SO 2 —NR G —,
 each of R G  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted or unsubstituted; 
 Y 1  is N or CR Y1 , 
 R Y1  is selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; 
 Y 2  is N or CR Y2 , 
 R Y2  is selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —N—(C 1-6 alkyl) 2 , —C 1-6  alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy; 
 when the “ ” in the term “Y 3   Y 4 ” represents a single bond, Y 3  is NR Y3 , and Y 4  is CO; 
 when the “ ” in the term “Y 3   Y 4 ” represents a double bond, Y 3  is N or CR Y3 , and Y 4  is N or CR Y4 ; 
 R Y3  and R Y4  are independently selected from hydrogen, deuterium, halogen, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH ,-C 1-6 alkylene—OH, —CONH 2  or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxyl; 
 T is absent, O, NR 1  or CRIR 2 ; 
 each of R 1  and R 2  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; or 
 R 1  and R 2  together with the carbon atom to which they are both attached form CO or C═NR 5 ; 
 p is 0, 1, 2 or 3; 
 each of R 3  and R 4  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; or 
 R 3  and R 4  together with the carbon atom to which they are both attached form a 3-12 membered heterocyclic ring or 5-12 membered heteroaromatic ring or C═NR 5 , and each of the ring systems is independently optionally substituted or unsubstituted; 
 each of R 5  is selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy; 
 q is 0, 1, 2, 3 or 4; 
 W is absent, —O, —S or —C(R W ) 2 —; and each of R W  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-6 alkyl, —CO—OC 1-6 alkyl, —C 1-6 alkyl-O—C 16 alkoxy, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; 
 ring C is absent, a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the ring systems is independently optionally substituted or unsubstituted; 
 when ring C is absent, Y 5  is CR 5a R 5b , NR 5a  or O, and Y 6  is CR 6a R 6b , NR 6a  or O; 
 when ring C is 5-12 membered aromatic ring, 5-12 membered heteroaromatic ring or 5-12 membered heterocyclic ring;
 i) Y 5  is CR 5a  or N, and Y 6  is CR 6a  or N, when the “ ” in the term “Y 5   Y 6 ” represents a single bond; or 
 ii) Y 5  is C, and Y 6  is C, when the “ ” in the term “Y 5   Y 6 ” represents a double bond; 
 
 each of R 5a  and R 5b  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; 
 each of R 6.  and R 6b  is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl; 
 each of R a  is independently hydrogen, deuterium, halogen, —NR a1 R a2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, —C 1-6 alkoxy, —C 1-6 alkyl, —C 3-8 cycloalkyl,-C 1-6 alkylene—NR a1 R a2 , —C 1-6 alkylene-O—C 1-6 alkyl, —C 1-6 alkylene—CO—OR a1 , —C 1-6 alkylene-(3-10 membered heterocyclic), —C 1-6 alkylene-(5-10 membered heteroaryl), —C 1-6 alkylene—CO—NR a1 R a2 , —C 1-6 alkylene - NR a1 —CO—NR a1 R a2 , —C 1-6 alkylene—NR a1 —CO—C 1-6 alkyl, —CO—NR a1 R a2 , —COO—C 1-6 alkyl, —CO—CO—NR a1 R. 2 , —C 3-10 carbocyclic, −5-10 membered heteroaryl, −3-10 membered heterocyclic, —CO—C 1-6 alkyl, —CO—C 1-6 alkylene—NR a1 R a2 , —CO—NR a1 -(3-10 membered heterocyclic), —CO—NR a1 -(3-10 membered heterocyclic), —CO-(3-10 membered heterocyclic), —O—C 1-6 alkylene—CO—OR a1 , —O—C 1-6 alkylene—CO—NR a1 R.2,—O—C 1-6 alkylene—NR a1 R a2 , —O—C 3-10 carbocyclic, —O-(3-10 membered heterocyclic), —NR a1 —CO—C 1-6 alkyl, —NR a1 —CO—NR a1 R. 2 , —NR—CO-(5-10 membered heteroaryl), —NR a1 —CO—C 3-8 cycloalkyl,—NR a1 —C 1-6 alkylene—NR a1 R a2 , —NR a1 —C 1-6 alkylene-(3-10 membered heterocyclic), —NR a1 —C 1-6 alkylene-(5-10 membered heteroaryl), —NR a1 —SO 2 C 1-6 alkyl, —S—C 1-6 alkyl, —SONR a1 R a2 , —SO 2 NR a1 R a2 , —SO—C 1-6 alkyl, —SO 2 C 1-6 alkyl, —PO(C 1-6 alkyl) 2 , —PO(C 1-6 alkoxy) 2 , −3-10 membered heterocyclic or −5-10 membered heteroaryl; each of which is independently optionally substituted; and n is 0, 1, 2, 3, 4, 5 or 6; or 
 two adjacent R a  can be joined together to form a 6-membered aryl ring, 5-membered heteroaryl ring, 6-membered heteroaryl ring, −3-6 membered heterocyclic or -3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted; or 
 R a  and R w  with the atom to which they are both attached form a 3-10 membered aromatic ring, 3-10 membered heteroaromatic ring or 3-10 membered heterocyclic ring; and each of the ring systems is independently optionally substituted; 
 each of R a1 and R a e is independently selected from hydrogen, deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
 
     
     
         233 . The compound or pharmaceutically acceptable salt thereof of  claim 232 , wherein X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         234 . The compound or pharmaceutically acceptable salt thereof of  claim 232  or  claim 233 , wherein X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         235 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 234 , wherein X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         236 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 235 , wherein X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         237 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 236 , wherein X 1  is N, S, NR X1 , C(R X1 ) 2 , or CR X1 ; each of R X1  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CONH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         238 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 237 , wherein X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; each of R X2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —CO—C 1-6 alkyl, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —SF 5 , —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene-C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         239 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 238  wherein X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; each of R X2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —CO—C 1-6 alkyl, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —SF 5 , —NHCO—C 3-8 cycloalkyl, —NH—C 3-8 cycloalkyl, —C 1-6 alkylene-(3-8 membered heterocyclyl), —NHCO-(5-12 membered heterocyclyl), —NH—C 1-6 alkylene—C 3-8 cycloalkyl or 3-8 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         240 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 239 , wherein X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; each of R X2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-4 alkyl, —C 1-3 alkoxy, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene-C 3-6 cycloalkyl or 3-6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         241 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 240 , wherein X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; each of R X2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, methoxy, ethoxy, propoxy, isopropoxy, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene-C 3-6 cycloalkyl, 3 membered heterocyclic, 4 membered heterocyclic, 5 membered heterocyclic or 6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         242 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 241 , wherein X 2  is N, S, NR X2 , C(R X2 ) 2 , CR X2  or CO; each of R X2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, methoxy, ethoxy, propoxy, isopropoxy, —CO—C 1-3 alkyl, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —SF 5 , —NHCO—C 3-6 cycloalkyl, —NH—C 3-6 cycloalkyl, —C 1-3 alkylene-(3-6 membered heterocyclyl), —NHCO-(5-10 membered heterocyclyl), —NH—C 1-3 alkylene-C 3-6 cycloalkyl, 3 membered heterocyclic, 4 membered heterocyclic, 5 membered heterocyclic or 6 membered heterocyclic, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, -oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         243 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 242 , wherein R X1  and R X2  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         244 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 243 , wherein R X1  and R X2  together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         245 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 244 , wherein R X1  and R X2  together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N or O, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         246 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 245 , wherein X 3  is N, S, O, NR X3 , C(R X3 ) 2  or CR X3;  each of R X3  is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl, —C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl or —O—C 1-6 alkylene-C 1-6 alkyl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         247 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 246 , wherein X 3  is N, S, O, NR X3 , C(R X3 ) 2  or CR X3;  each of R X3  is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-6 alkyl, —C 1-6 alkoxy, C 3-8 cycloalkyl, C 5-8 aryl, —S—C 1-6 alkyl, 3-12 membered heterocyclyl, —O—C 3-8 cycloalkyl or —O—C 1-6 alkylene-C 1-6 alkyl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         248 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 247 , wherein X 3  is N, S, O, NR X3 , C(R X3 ) 2  or CR X3;  each of R X3  is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , —C 1-3 alkyl,—C 1-3 alkoxy, C 3-6 cycloalkyl, C 5-8 aryl, -S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl or —O—C 1-3 alkylene—C 1-3 alkyl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         249 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 248 , wherein X 3  is N, S, O, NR X3 , C(R X3 ) 2  or CR X3;  each of R X3  is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, C 3-6 cycloalkyl, C 5-8 aryl, —S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl or —O—C 1-3 alkylene-C 1-3 alkyl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         250 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 249 , wherein X 3  is N, S, O, NR X3 , C(R X3 ) 2  or CR X3;  each of R X3  is independently selected from hydrogen, deuterium, F, Cl, Br, carboxyl, —NO 2 , —NH 2 , —CN, —CONH 2 , methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, C 3-6 cycloalkyl, C 5-8 aryl, —S—C 1-3 alkyl, 3-10 membered heterocyclyl, —O—C 3-6 cycloalkyl or —O—C 1-3 alkylene —C 1-3 alkyl, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         251 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 250 , wherein R X2  and R X3  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         252 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 251 , wherein R X2  and R X3  together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         253 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 252 , wherein R X2  and R X3  together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N or O, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         254 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 253 , wherein X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; each of R X4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or 5-12 membered heteroaryl and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         255 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 254 , wherein X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; each of R X4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NHCO-(5-12 membered heterocyclyl) or 5-12 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         256 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 255 , wherein X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; each of R X4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl,—C 1-3 alkoxy, —NHCO-(5-10 membered heterocyclyl) or 5-10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         257 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 256 , wherein X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; each of R X4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NHCO-(5-10 membered heterocyclyl), 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl or 10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         258 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 257 , wherein X 4  is N, S, NR X4 , C(R X4 ) 2  or CR X4 ; each of R X4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NHCO-(5-10 membered heterocyclyl), 5 membered heteroaryl, 6 membered heteroaryl, 7 membered heteroaryl, 8 membered heteroaryl, 9 membered heteroaryl or 10 membered heteroaryl, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, oxo, ═O, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         259 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 258 , wherein R X3  and R X4  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         260 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 259 , wherein R X3  and R X4  together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         261 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 260 , wherein R X3  and R X4  together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         262 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 261 , wherein X 5  is N, S, NR X5  C(R X5 ) 2  or CR X5 ; each of R X5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         263 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 262 , wherein X 5  is N, S, NR X5  C(R X5 ) 2  or CR X5 ; each of R X5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         264 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 263 , wherein X 5  is N, S, NR X5  C(R X5 ) 2  or CR X5 ; each of R X5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         265 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 264 , wherein X 5  is N, S, NR X5  C(R X5 ) 2  or CR X5 ; each of R X5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         266 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 265 , wherein X 5  is N, S, NR X5 C(R X5 ) 2  or CR X5 ; each of R X5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted with 1, 2 or 3 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         267 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 266 , wherein R X4  and R X5  together with the ring to which they are attached form a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         268 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 267 , wherein R X4  and R X5  together with the ring to which they are attached form a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         269 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 268 , wherein R X4  and R X5  together with the ring to which they are attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring or a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         270 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 269 , wherein ring A is selected from 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         271 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 270 , wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, 
       
         
           
           
               
               
           
         
       
       —C(R G ) 2 — or —SO 2 —NR G —;
 each of R G  is independent selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy, and each of which is independently optionally substituted or unsubstituted. 
 
     
     
         272 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 271 , wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, 
       
         
           
           
               
               
           
         
       
       —C(R G ) 2 — or —SO 2 —NR G —;
 each of R G  is independent selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-3 alkyl or —C 1-3 alkoxy, and each of which is independently optionally substituted or unsubstituted. 
 
     
     
         273 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 272 , wherein G is selected from absent, S, —SO—, —SO 2 —, O, —CO—, —NR G —, 
       
         
           
           
               
               
           
         
       
       —C(R G ) 2 — or −502—NR G —;
 each of R G  is independent selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy, and each of which is independently optionally substituted or unsubstituted. 
 
     
     
         274 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 273 , wherein Y 1  is N or CR Y1 ; R Y1  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, -C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, -C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         275 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 274 , wherein Y 1  is N or CR Y1 ; R Y1  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6 alkenyl, —C 3-8 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         276 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 275 , wherein Y 1  is N or CR Y1 ; R Y1  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl, —C 1-3 alkoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         277 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 276 , wherein Y 1  is N or CR Y1 ; R Y1  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         278 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 277 , wherein Y 2  is N or CR Y2 ; R Y2  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6  alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         279 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 278 , wherein Y 2  is N or CR Y2 ; R Y2  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —NH—C 1-6 alkyl, —N—(C 1-6 alkyl) 2 , —C 1-6  alkenyl, —C 3-8 cycloalkyl or —C 5-10 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         280 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 279 , wherein Y 2  is N or CR Y2 ; R Y2  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —C 1-3 alkyl, —C 1-3 alkoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         281 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 280 , wherein Y 2  is N or CR Y2 ; R Y2  is selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, —NH—C 1-3 alkyl, —N—(C 1-3 alkyl) 2 , —C 1-3 alkenyl, —C 3-6 cycloalkyl or —C 5-8 aryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         282 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 281 , wherein R Y3  and R Y4  are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH , —C 1-6 alkylene—OH, —CONH 2  or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         283 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 282 , wherein R Y3  and R Y4  are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-6 alkyl, carboxyl, —COO—C 1-6 alkyl, —NH—C 1-6 alkylene—OH ,-C 1-6 alkylene—OH, —CONH 2  or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         284 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 283 , wherein R Y3  and R Y4  are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, —C 1-3 alkyl, carboxyl, —COO—C 1-3 alkyl, —NH—C 1-3 alkylene—OH ,—C 1-3 alkylene—OH, —CONH 2  or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         285 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 284 , wherein R Y3  and R Y4  are independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —OH, —CN, methyl, ethyl, propyl, isopropyl, carboxyl, —COO—C 1-3 alkyl, —NH—C 1-3 alkylene—OH ,—C 1-3 alkylene—OH, —CONH 2  or −5-8 membered heteroaryl, and each of which is independently optionally substituted with 1, 2, 3, 4, 5, or 6 substituents, and the said each substituents is independently selected from deuterium, F, Cl, Br, I, —NH 2 , —CN, —OH, —NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         286 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 285 , wherein ring B is selected from 
       
         
           
           
               
               
           
         
       
     
     
         287 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 286 , wherein each of R 1  and R 2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
     
     
         288 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 287 , wherein each of R 1  and R 2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-3 alkyl, —N(C 1-3 alkyl) 2 , substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl. 
     
     
         289 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 288  wherein each of R 1  and R 2  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         290 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 289 , wherein each of R 1  and R 2  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         291 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 290 , wherein R 1  and R 2  together with the carbon atom to which they are both attached form CO or C═NR 5.    
     
     
         292 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 291 , wherein R 1  and R 2  together with the carbon atom to which they are both attached form CO. 
     
     
         293 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 292 , wherein R 1  and R 2  together with the carbon atom to which they are both attached form C═NR 5 . 
     
     
         294 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 293 , wherein each of R 3  and R 4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
     
     
         295 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 294 , wherein each of R 3  and R 4  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —NH—C 1-3 alkyl, —N(C 1-3 alkyl) 2 , substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted 
     
     
         296 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 295  wherein each of R 3  and R 4  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         297 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 296 , wherein each of R 3  and R 4  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; —NH—C 1-3 alkyl; —N(C 1-3 alkyl) 2 ; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         298 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 297 , wherein R 3  and R 4  together with the carbon atom to which they are both attached form 3-12 membered heterocyclic ring or 5-12 membered heteroaromatic ring or C═NR 5 ; and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         299 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 298 , wherein R 3  and R 4  together with the carbon atom to which they are both attached form 3-10 membered heterocyclic ring or 5-10 membered heteroaromatic ring or C═NR 5 ; and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         300 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 299 , wherein R 3  and R 4  together with the carbon atom to which they are both attached form 3 membered heterocyclic ring, 4 membered heterocyclic ring, 5 membered heterocyclic ring, 6 membered heterocyclic ring, 7 membered heterocyclic ring, 8 membered heterocyclic ring, 9 membered heterocyclic ring, 10 membered heterocyclic ring, 5 membered heteroaromatic ring, 6 membered heteroaromatic ring, 7 membered heteroaromatic ring, 8 membered heteroaromatic ring, 9 membered heteroaromatic ring, 10 membered heteroaromatic ring or C═NR 5 , and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         301 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 300 , wherein each of R 5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         302 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 301 , wherein each of R 5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         303 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 302 , wherein each of R 5  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         304 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 303 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-6 alkyl, —CO—OC 1-6 alkyl, —C 1-6 alkyl-O—C 1-6 alkoxy, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
     
     
         305 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 304 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —CO—C 1-3 alkyl, —CO—OC 1-3 alkyl, —C 1-3 alkyl—O—C 1-3 alkoxy, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl 
     
     
         306 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 305 , wherein W is absent, —O, —S or —C(R W ) 2 -; and each of R W  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkyl—O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         307 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 306 , wherein W is absent, —O, —S or —C(R W ) 2 —; and each of R W  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkyl—O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         308 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 307 , wherein W is absent, —O, —S or —C(R W ) 2 -; and each of R W  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN;—OH; —NO 2 ; carboxyl; —CO—C 1-3 alkyl; —CO—OC 1-3 alkyl; —C 1-3 alkyl—O—C 1-3 alkoxy; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         309 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 308 , wherein ring C is absent, a 5-12 membered aromatic ring, a 5-12 membered heteroaromatic ring or a 5-12 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         310 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 309 , wherein ring C is absent, a 5-10 membered aromatic ring, a 5-10 membered heteroaromatic ring or a 5-10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         311 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 310 , wherein ring C is absent, a 5 membered aromatic ring, a 6 membered aromatic ring, a 7 membered aromatic ring, an 8 membered aromatic ring, a 9 membered aromatic ring, a 10 membered aromatic ring, a 5 membered heteroaromatic ring, a 6 membered heteroaromatic ring, a 7 membered heteroaromatic ring, an 8 membered heteroaromatic ring, a 9 membered heteroaromatic ring, a 10 membered heteroaromatic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 7 membered heterocyclic ring, an 8 membered heterocyclic ring, a 9 membered heterocyclic ring, a 10 membered heterocyclic ring, and each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the ring systems is independently optionally substituted or unsubstituted. 
     
     
         312 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 311 , wherein ring C is selected from 
       
         
           
           
               
               
           
         
       
     
     
         313 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 312 , wherein each of R 5a  and R 5b  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
     
     
         314 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 313 , wherein each of R 5a  and R 5b  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl. 
     
     
         315 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 314 , wherein each of R 5a  and R 5b  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         316 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 315 , wherein each of R Ya  and R 5b  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ;
 —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
 
     
     
         317 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 316 , wherein each of R 6a  and R 6b  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted —C 1-6 alkyl. 
     
     
         318 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 317 , wherein each of R 6a  and R 6b  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl. 
     
     
         319 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 318 , wherein each of R 6a  and R 6b  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         320 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 319 , wherein each of R 6a  and R 6b  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         321 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 320 , wherein each of R a  is independently selected from hydrogen, deuterium, F, Cl, Br, —NR a1 R a2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, —C 1-3 alkoxy,—C 1-4 alkyl, —C 3-6 cycloalkyl, —C 1-3 alkylene—NR a1 R a2 , —C 1-3 alkylene-O—C 1-6 alkyl, —C 1-3 alkylene—CO—OR a1 , —C 1-3 alkylene-(3-8 membered heterocyclic), —C 1-3 alkylene-(5-8 membered heteroaryl), —C 1-3 alkylene—CO—NR a1 R a2 , —C 1-3 alkylene—NR a1 —CO—NR a1 R a2 , —C 1-3 alkylene—NR a1 —CO—C 1-3 alkyl, —CO—NR a1 R a2 , —CO—CO—NR a1 R a2 , —C 3-8 carbocyclic, −3-8 membered heterocyclic, —CO—C 1-3 alkyl, —COO—C 1-3 alkyl, —CO—C 1-3 alkylene—NR a1 R a2 , —CO—NR a1 -(3-8 membered heterocyclic), —CO—NR a1 -(3-8 membered heterocyclic), —CO-(3-8 membered heterocyclic), —O—C 1-3 alkylene-CO—OR a1 , —O—C 1-3 alkylene-CO—NR a1 R a2 ,  - 0  - C 1-3 alkylene-NR a1 R a2 , —O—C 3-8 carbocyclic, —O-(3-8 membered heterocyclic), —NR a1 —CO—C 1-3 alkyl, —NR a1 —CO—NR a1 R a2 , —NR a1 —CO-(5-8 membered heteroaryl), —NR a1 —CO—C 3-6 cycloalkyl,—NR a1 —C 1-3 alkylene—NR a1 R a2 , —NR a1 —C 1-3 alkylene-(3-8 membered heterocyclic), —NR a1 —C 1-3 alkylene-(5-8 membered heteroaryl), —NR a1 —SO 2 C 1-3 alkyl, —SONR a1 R a2 , —SO 2 NR a1 R a2 , —SO—C 1-3 alkyl, —SO 2 C 1-3 alkyl, —PO(C 1-3 alkyl) 2 , —PO(C 1-3 alkoxy) 2 , −3-8 membered heterocyclic or −5-8 membered heteroaryl; each of which is independently optionally substituted; and n is 0, 1, 2, 3, 4, 5 or 6. 
     
     
         322 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 321 , wherein each of R a  is independently selected from hydrogen, deuterium, F, Cl, Br, —NR a1 R. 2 , —CN, —OH, —NO 2 , oxo, ═O, carboxyl, methoxy, ethoxy, propoxy, isopropoxy methyl, ethyl, propyl, isopropyl, butyl, isobutyl, —C 3-6 cycloalkyl,-C 1-3 alkylene - NR a1 R a2 , —C 1-3 alkylene-(3-8 membered heterocyclic), —C 1-3 alkylene-(5-8 membered heteroaryl), - 3 alkylene - CO - NR a1 R a2 , - 3 alkylene - NR a1   - CO - NR a1 R a2 , —CO—NR a1 R a2 , —CO—CO—NR a1 R a2 , —C 3-8 carbocyclic, −3-8 membered heterocyclic, —CO—C 1-3 alkyl, —CO—C 1-3 alkylene—NR a1 R a2 , —CO—NR.1-(3-8 membered heterocyclic), —CO—NR a1 -(3-8 membered heterocyclic), —CO-(3-8 membered heterocyclic), —O—C 1-3 alkylene-CO—OR a1 , —O—C 1-3 alkylene—CO—NR a1 R a2 , —O—C 1-3 alkylene-NR a1 R a2 , —O—C 3-8 carbocyclic, —O-(3-8 membered heterocyclic), —NR a1 —CO—C 1-3 alkyl, —NR a1 —CO-(5-8 membered heteroaryl), —NR a1 —CO—C 3-6 cycloalkyl,—NR a1 —C 1-3 alkylene—NR a1 R a2 , —NR a1 —C 1-3 alkylene-(3-8 membered heterocyclic), —NR a1 —C 1-3 alkylene-(5-8 membered heteroaryl), —NR a1 —SO 2 C 1-3 alkyl, —SONR a1 R a2 , —SO 2 NR a1 R a2 , —SO 2 C 1-3 alkyl, —PO(C 1-3 alkyl) 2 , —PO(C 1-3 alkoxy) 2 , −3-8 membered heterocyclic or −5-8 membered heteroaryl; each of which is independently optionally substituted; and n is 0, 1, 2, 3, 4, 5 or 6. 
     
     
         323 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 322 , wherein each of R a1 and R a e is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-6 alkoxy, or substituted or unsubstituted 
     
     
         324 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 323 , wherein two adjacent R a  can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3-6 membered heterocyclic ring or a 3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted with deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         325 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 324 , wherein two adjacent R a  can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3-6 membered heterocyclic ring or a 3-6 membered carbocyclic ring, wherein each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         326 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 325 , wherein two adjacent R a  can be joined together to form a 6-membered aromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 3 membered heterocyclic ring, a 4 membered heterocyclic ring, a 5 membered heterocyclic ring, a 6 membered heterocyclic ring, a 3 membered carbocyclic ring, a 4 membered carbocyclic ring, a 5 membered carbocyclic ring, a 6 membered carbocyclic ring, wherein each of the heteroaryl contains 1, 2 or 3 heteroatoms selected from N, O or S, and each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S, each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         327 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 326 , R a  and R w  with the atom to which they are both attached form a 3-10 membered aromatic ring, a 3-10 membered heteroaromatic ring or a 3-10 membered heterocyclic ring; and each of the ring systems is independently optionally substituted with deuterium, halogen, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-6 alkyl or —C 1-6 alkoxy. 
     
     
         328 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 327 , R a  and R w  with the atom to which they are both attached form a 3-10 membered aromatic ring, a 3-10 membered heteroaromatic ring or a 3-10 membered heterocyclic ring; and each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         329 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 328 , R a  and R w  with the atom to which they are both attached form a 3-10 membered aromatic ring, a 3-10 membered heteroaromatic ring or a 3-10 membered heterocyclic ring; each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S; each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S; and each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         330 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 329 , R a  and R w  with the atom to which they are both attached form a 5 membered aromatic ring, a 6 membered aromatic ring, a 5 membered heteroaryl ring, a 6 membered heteroaryl ring, a 5 membered heterocyclic ring or a 6 membered heterocyclic ring; each of the heteroaromatic ring contains 1, 2 or 3 heteroatoms selected from N, O or S; each of the heterocyclic ring contains 1, 2 or 3 heteroatoms selected from N, O or S; and each of the ring systems is independently optionally substituted with deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, —C 1-3 alkyl or —C 1-3 alkoxy. 
     
     
         331 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 330 , wherein each of R a1  and R a2  is independently selected from hydrogen, deuterium, F, Cl, Br, —NH 2 , —CN, —OH, —NO 2 , carboxyl, substituted or unsubstituted —C 1-3 alkoxy, or substituted or unsubstituted —C 1-3 alkyl. 
     
     
         332 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 331 , wherein each of R a1 and R a2  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with halogen, NH 2 , CN, OH, NO 2 , carboxyl, C 1-3 alkyl or C 1-3 alkoxy. 
     
     
         333 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 332 , wherein each of R a1 and R a2  is independently selected from hydrogen; deuterium; F; Cl; Br; —NH 2 ; —CN; —OH; —NO 2 ; carboxyl; methoxy; ethoxy; propoxy; isopropoxy; —C 1-3 alkoxy substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy; methyl; ethyl; propyl; isopropyl; —C 1-3 alkyl substituted with F, Cl, Br, NH 2 , CN, OH, NO 2 , carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy. 
     
     
         334 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 333 , wherein the compound is of Formula III-a: 
       
         
           
           
               
               
           
         
         Wherein X 1 , X 2 , X 3 , X 4 , X 5 ; G, R Y3 , T, R 3 , R 4 , W, Y 5 ; Y 6 , R a , p, q and n are as defined in  claims 232 - 333 . 
       
     
     
         335 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 334 , wherein the compound is of Formula III-b: 
       
         
           
           
               
               
           
         
         Wherein X 1 , X 2 , X 3 , X 4 , X 5 ; G, R Y3 , T, R 3 , R 4 , W, Y 5 ; Y 6 , R a , p, q and n are as defined in  claims 232 - 334 . 
       
     
     
         336 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 335 , wherein the compound is of Formula III-c: 
       
         
           
           
               
               
           
         
         Wherein X 1 , X 2 , X 3 , X 4 , X 5 , G, R Y3 , T, R 3 , R 4 , W, Y 5 , Y 6 , R a , p, q and n are as defined in  claims 232 - 335 . 
       
     
     
         337 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 336 , wherein the compound is of Formula III-d: 
       
         
           
           
               
               
           
         
         Wherein X 1 , X 2 , X 3 , X 4 , X 5 ; G, R Y3 , T, R 3 , R 4 , W, Y 5 ; Y 6 , R a , p, q and n are as defined in  claims 232 - 336 . 
       
     
     
         338 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 232 - 337 , wherein the compound is of Formula III-e: 
       
         
           
           
               
               
           
         
         Wherein X 1 , X 2 , X 3 , X 4 , X 5 , G, R Ya , T, R 3 , R 4 , W, Y 5 , Y 6 , R a , p, q and n are as defined in  claims 232 - 337 . 
       
     
     
         339 . The compound or pharmaceutically acceptable salt thereof of any one of  claims 1 - 338 , wherein the compound is selected from 
       
         
           
                 
                 
               
                     
                 
                   1 
                   ethyl (S)-3-(1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-(2,3-dichlorophenyl)-5--2- 
                 
                     
                   carboxylate 
                 
                   2 
                   (S)-1′-(5-(2,3-dichlorophenyl)-6-methylpyrazin-2-yl)-5,7-dihydrospiro[cyclopenta[b]pyridine- 
                 
                     
                   6,4′-piperidin]-5-amine 
                 
                   3 
                   (S)-3-(1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-(2,3-dichlorophenyl)-5- 
                 
                     
                   methylpyrazine-2-carboxylic acid 
                 
                   4 
                   (S)-3-(1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-(2,3-dichlorophenyl)-5- 
                 
                     
                   methylplyrazine-2-carboxamide 
                 
                   5 
                   ethyl (S)-3-(1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-((2-amino-3-chloropyridin- 
                 
                     
                   4-yl)thio)-5-methylpyrazine-2-carboxylate 
                 
                   6 
                   (S)-1′-(5-((2-amino-3-chloropyridin-4-yl)thio)-6-methylpyrazin-2-yl)-1,3-dihydrospiro[indene-2 
                 
                     
                   4′-piperidin]-1-amine 
                 
                   7 
                   (S)-1′-(6-amino-5-((2,3-dichlorophenyl)thio)pyrazin-2-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine 
                 
                   8 
                   (S)-1′-(4-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyrimidin-2-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine 
                 
                   9 
                   (S)-1′-(5-((2-amino-3-chloropyridin-4-yl)thio)pyridin-2-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine 
                 
                   10 
                   (S)-1′-(5-((2-amino-3-chloropyridin-4-yl)thio)-6-(methylamino)pyrazin-2-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine 
                 
                   11 
                   (S)-1′-(5-((2-amino-3-chloropyridin-4-yl)thio)-6-(dimethylamino)pyrazin-2-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine 
                 
                   12 
                   (S)-1′-(6-amino-5-(thiazol-4-ylthio)pyrazin-2-yl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′- 
                 
                     
                   piperidin]-5-amine 
                 
                   13 
                   (S)-1′-(6-amino-5-(thiazol-2-ylthio)pyrazin-2-yl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′- 
                 
                     
                   piperidin]-5-amine 
                 
                   14 
                   (S)-1′-(6-amino-5-(quinolin-3-ylthio)pyrazin-2-yl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′- 
                 
                     
                   piperidin]-5-amine 
                 
                   15 
                   (S)-5-amino-1′-(5-((2-amino-3-chloropyridin-4-yl)thio)pyridin-2-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidine]-3-carbonitrile 
                 
                   16 
                   (S)-1′-(5-((2-ammo-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-N-methyl-1,3-dihydrospiro[indene- 
                 
                     
                   2,4′-piperidin]-1-amine 
                 
                   17 
                   (S)-1′-(5-((3,5-dichloropyridin-4-yl)thio)pyrazin-2-yl)-5,6,7-trifluoro-1,3-dihydrospiro[indene- 
                 
                     
                   2,4′-piperidin]-1-amine 
                 
                   18 
                   (S)-1-amino-1′-(2-((2-cyanopyridin-3-yl)thio)pyrimidin-5-yl)-1,3-dihydrospiro[indene-2,4′- 
                 
                     
                   piperidine]-4-carbonitrile 
                 
                   19 
                   (S)-1′-(5-((3-chloro-2-methoxypyridin-4-yl)thio)pyrazin-2-yl)-6-(methylthio)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   20 
                   (S)-1-(5-((5-(4-amino-2-(tert-butyl)-4,6-dihydrospiro[cyclopenta[b]thiophene-5,4′-piperidin]-1′- 
                 
                     
                   yl)pyrazin-2-yl)thio)-2-chlorophenyl)ethan-1-one 
                 
                   21 
                   (S)-1′-(5-((3-chloro-2-(isopropylamino)pyridin-4-yl)thio)pyrazin-2-yl)-6-(methylsulfonyl)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   22 
                   (S)-1′-(5-((2-amino-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-7,7-d2-5-amine 
                 
                   23 
                   (S)-(3-(1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-(2,3-dichlorophenyl)-5- 
                 
                     
                   methylpyrazin-2-yl)methanol 
                 
                   24 
                   (S)-(3-(1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-((2-amino-3-chloropyridin-4- 
                 
                     
                   yl)thio)-5-methylpyrazin-2-yl)methanol 
                 
                   25 
                   (S)-1′-(3-bromo-5-(2,3-dichlorophenyl)-6-methylpyrazin-2-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine 
                 
                   26 
                   (S)-3-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-6-(2,3- 
                 
                     
                   dichlorophenyl)-5-methylpyrazine-2-carbonitrile 
                 
                   27 
                   (S)-3-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-6-(2,3- 
                 
                     
                   dichlorophenyl)-5-methylpyrazine-2-carboxamide 
                 
                   28 
                   (S)-3-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-6-(2,3- 
                 
                     
                   dichlorophenyl)-5-methylpyrazin-2-ol 
                 
                   29 
                   (S)-1′-(6-amino-3-bromo-5-((2,3-dichlorophenyl)thio)pyrazin-2-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine 
                 
                   30 
                   (S)-5-amino-3-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-6-((2,3- 
                 
                     
                   dichlorophenyl)thio)pyrazine-2-carbonitrile 
                 
                   31 
                   (S)-5-amino-3-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-6-((2,3- 
                 
                     
                   dichlorophenyl)thio)pyrazine-2-carboxamide 
                 
                   32 
                   (S)-1′-(6-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyridin-2-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine 
                 
                   33 
                   (S)-1′-(6-((2-amino-3-chloropyridin-4-yl)thio)pyridin-3-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine 
                 
                   34 
                   (S)-1′-(4-((2-amino-3-chloropyridin-4-yl)thio)phenyl)-5,7-dihydrospiro[cyclopenta[b]pyridine- 
                 
                     
                   6,4′-piperidin]-5-amine 
                 
                   35 
                   (S)-1′-(4-((2-amino-3-chloropyridin-4-yl)thio)isoquinolin-1-yl)-1,3-dihydrospiro[indene-2,4′- 
                 
                     
                   piperidin]-1-amine 
                 
                   36 
                   (S)-6-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-3-(2,3- 
                 
                     
                   dichlorophenyl)-5-methyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 
                 
                   37 
                   (S)-6-(1-amino-6-fluoro-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-(2,3-dichlorophenyl)- 
                 
                     
                   5-methyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 
                 
                   38 
                   (S)-6-(1-amino-5,6,7-trifluoro-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-methyl-3-(5- 
                 
                     
                   methylthiophen-2-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 
                 
                   39 
                   (S)-2-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-5-(2,3- 
                 
                     
                   dichlorophenyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one 
                 
                   40 
                   (S)-6-amino-2-(1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-((2-amino-3- 
                 
                     
                   chloropyridin-4-yl)thio)-3-methylpyrimidin-4(3H)-one 
                 
                   41 
                   (S)-1′-(6-amino-5-((4-chlorothiazol-2-yl)thio)pyrazin-2-yl)-4,6- 
                 
                     
                   dihydrospiro[cyclopenta[d]thiazole-5,4′-piperidin]-4-amine 
                 
                   42 
                   (S)-1-amino-1′-(5-((4-amino-5-bromopyrimidin-2-yl)thio)-1-methyl-6-oxo-1,6-dihydropyridin-2- 
                 
                     
                   yl)-1,3-dihydrospiro[indene-2,4′-piperidine]-6-carbonitrile 
                 
                   43 
                   (S)-6-(1-amino-6-bromo-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-((3-chloro-2- 
                 
                     
                   methoxypyridin-4-yl)thio)-1-methylpyridin-2(1H)-one 
                 
                   44 
                   (S)-1-amino-1′-(4-(6-bromonaphthalen-2-yl)thiazol-2-yl)-1,3-dihydrospiro[indene-2,4′- 
                 
                     
                   piperidine]-6-carbonitrile 
                 
                   45 
                   (S)-1′-(6-amino-5-(2-chloro-3-methylphenyl)pyrazin-2-yl)-6-bromo-1,3-dihydrospiro[indene-2,4′- 
                 
                     
                   piperidin]-1-amine 
                 
                   46 
                   (S)-1′-(5-(3-amino-2-(trifluoromethyl)phenyl)pyrimidin-2-yl)-1,3-dihydrospiro[indene-2,4′- 
                 
                     
                   piperidine]-1,6-diamine 
                 
                   47 
                   (S)-1′-(6-amino-5-(2-chloro-3-methylphenyl)pyrazin-2-yl)-1,3-dihydrospiro[indene-2,4′- 
                 
                     
                   piperidine]-1,6-diamine 
                 
                   48 
                   (S)-1′-(6-(5-chlorothiophen-2-yl)pyridazin-3-yl)-5-methyl-1,3-dihydrospiro[indene-2,4′- 
                 
                     
                   piperidin]-1-amine 
                 
                   49 
                   (S)-1′-(6′-chloro-[3,3′-bipyridazin]-6-yl)-5-methyl-1,3-dihydrospiro[indene-2,4′-piperidin]-1- 
                 
                     
                   amine 
                 
                   50 
                   (S)-1′-(3-(3,4-dihydro-1,5-naphthyridin-1(2H)-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   51 
                   (R)-1′-(5-(2,3-dichloro-5-methoxyphenyl)pyridin-2-yl)-2,3-dihydrospiro[indene-1,4′-piperidin]- 
                 
                     
                   2-amine 
                 
                   52 
                   (S)-6′-(1-amino-4-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-1′-methyl-2′-oxo-1′,2′- 
                 
                     
                   dihydro-[3,3′-bipyridine]-2-carbonitrile 
                 
                   53 
                   (S)-6′-(1-amino-4-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-1′-methyl-2′-oxo-1′,2′- 
                 
                     
                   dihydro-[3,3′-bipyridine]-2-carboxamide 
                 
                   54 
                   (S)-1′-(4-(3-methoxyphenyl)cyclohexyl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]- 
                 
                     
                   5-amine 
                 
                   55 
                   (S)-1-amino-1′-(6-((3-amino-2-chlorophenyl)thio)-1,2,4-triazin-3-yl)-1,3-dihydrospiro[indene- 
                 
                     
                   2,4′-piperidine]-6-carbonitrile 
                 
                   56 
                   1-(5-((5-((1S)-1-amino-6-(methylsulfmyl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)pyrazin- 
                 
                     
                   2-yl)thio)-2-chlorophenyl)ethan-1-one 
                 
                   57 
                   (S)-1′-(5-(pyrimidin-2-ylthio)pyrazin-2-yl)-6-(trifluoromethyl)-1,3-dihydrospiro[indene-2,4′- 
                 
                     
                   piperidin]-1-amine 
                 
                   58 
                   (S)-6-bromo-5-fluoro-1′-(5-(quinolin-4-ylthio)pyrazin-2-yl)-1,3-dihydrospiro[indene-2,4′- 
                 
                     
                   piperidin]-1-amine 
                 
                   59 
                   (S)-6-(4-amino-4,6-dihydrospiro[cyclopenta[b]thiophene-5,4′-piperidin]-1′-yl)-3-(3- 
                 
                     
                   (trifluoromethyl)pyridin-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 
                 
                   60 
                   (S)-2-(1-amino-6-chloro-5-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-(3,5- 
                 
                     
                   dichloropyridin-4-yl)-3-methyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one 
                 
                   61 
                   (S)-1′-(7-(5-chloropyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-3-yl)-1,3- 
                 
                     
                   dihydrospiro[cyclopenta[a]naphthalene-2,4′-piperidin]-3-amine 
                 
                   62 
                   (S)-1′-(7-(3-chloropyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-3-yl)-1H,3H-spiro[phenalene-2,4′- 
                 
                     
                   piperidin]-1-amine 
                 
                   63 
                   (R)-1′-(3-(2-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-3,4-dihydro-1H- 
                 
                     
                   spiro[naphthalene-2,4′-piperidin]-3-amine 
                 
                   64 
                   (S)-6-amino-2-(1-amino-7-bromo-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-methyl-5- 
                 
                     
                   phenylpyrimidin-4(3H)-one 
                 
                   65 
                   (S)-1-amino-1′-(4-amino-6-oxo-5-(pyridazin-3-ylthio)-1,6-dihydropyrimidin-2-yl)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidine]-7-carbonitrile 
                 
                   66 
                   (S)-1-amino-1′-(1-methyl-6-oxo-5-(pyrazin-2-yl)-1,6-dihydropyrimidin-2-yl)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidine]-7-carbonitrile 
                 
                   67 
                   (S)-2-(1-amino-6-chloro-5-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-((4- 
                 
                     
                   isopropylphenyl)thio)pyrimidin-4(3H)-one 
                 
                   68 
                   (S)-4-amino-6-(1-amino-6-bromo-5-fluoro-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-(2- 
                 
                     
                   chloro-3-methylphenyl)-1-methylpyridin-2(1H)-one 
                 
                   69 
                   (S)-6-(4-acetyl-1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-4-amino-3-(4- 
                 
                     
                   (trifluoromethyl)phenyl)pyridin-2(1H)-one 
                 
                   70 
                   (S)-6′-(1-amino-4-hydroxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-2′-oxo-1′,2′-dihydro- 
                 
                     
                   [3,3′-bipyridine]-2-carbonitrile 
                 
                   71 
                   (S)-1′-(3-bromo-5-(1H-indol-6-yl)-6-methylpyrazin-2-yl)-4,6- 
                 
                     
                   dihydrospiro[cyclopenta[d]thiazole-5,4′-piperidin]-4-amine 
                 
                   72 
                   (S)-3-(4-amino-4,6-dihydrospiro[cyclopenta[d]thiazole-5,4′-piperidin]-1′-yl)-5-methyl-6-(2- 
                 
                     
                   oxoindolin-7-yl)pyrazine-2-carbonitrile 
                 
                   73 
                   (S)-1′-(5-amino-6-((2-amino-3-chloropyridin-4-yl)thio)-1,2,4-triazin-3-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine 
                 
                   74 
                   (S)-1′-(5-amino-6-((2-amino-3-chloropyridin-4-yl)thio)pyridin-3-yl)-6-chloro-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   75 
                   (S)-1′-(4-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyridin-2-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine 
                 
                   76 
                   (S)-1′-(5-((2,3-dichlorophenyl)thio)thiazol-2-yl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′- 
                 
                     
                   piperidin]-7-amine 
                 
                   77 
                   (R)-1′-(4-((3-chloropyridin-4-yl)thio)thiazol-2-yl)spiro[indoline-2,4′-piperidin]-3-amine 
                 
                   78 
                   (R)-1′-(2-(7-chloro-1H-indol-1-yl)thiazol-4-yl)-2,3-dihydrospiro[indene-1,4′-piperidin]-2-amine 
                 
                   79 
                   (R)-1′-(2-((2-(trifluoromethyl)phenyl)thio)thiazol-5-yl)-3H-spiro[benzofuran-2,4′-piperidin]-3- 
                 
                     
                   amine 
                 
                   80 
                   (S)-(5-(1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)pyrazin-2-yl)(2,3- 
                 
                     
                   dichlorophenyl)methanone 
                 
                   81 
                   (S)-2-(1-amino-6-fluoro-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-(indolin-1-yl)-3-methyl- 
                 
                     
                   3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one 
                 
                   82 
                   (S)-1′-(5-((1,2,3,4-tetrahydroquinolin-8-yl)thio)pyrazin-2-yl)-1,3- 
                 
                     
                   dihydrospiro[cyclopenta[b]naphthalene-2,4′-piperidin]-1-amine 
                 
                   83 
                   (S)-1′-(5-((2-amino-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-1,3- 
                 
                     
                   dihydrospiro[cyclopenta[a]naphthalene-2,4′-piperidin]-1-amine 
                 
                   84 
                   1′-(5-((3-amino-2-chlorophenyl)thio)-6-methylpyrazin-2-yl)-1-methyl-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   85 
                   (R)-1′-(7-((2-amino-3-chloropyridin-4-yl)thio)-1H-indol-4-yl)-3H-spiro[benzofuran-2,4′- 
                 
                     
                   piperidin]-3-amine 
                 
                   86 
                   (S)-1′-(7-((2-amino-3-chloropyridin-4-yl)thio)isoquinolin-3-yl)-5,6-dibromo-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   87 
                   (S)-4-((5-(5-acetyl-1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-aminopyrazin-2- 
                 
                     
                   yl)thio)-3-chloro-1-methylpyridin-2(1H)-one 
                 
                   88 
                   (S)-5-(1-amino-6-bromo-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-2-((2,3-dichlorophenyl)thio)- 
                 
                     
                   6-(hydroxymethyl)pyridin-3-ol 
                 
                   89 
                   (S)-6-bromo-1′-(5-(2,3-dichlorophenyl)-6-methylimidazo[1,5-a]pyrazin-8-yl)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   90 
                   (S)-1′-(7-((2-amino-3-chloropyridin-4-yl)thio)-[1,2,5]thiadiazolo[3,4-c]pyridin-4-yl)-6-bromo-1,3- 
                 
                     
                   dihydrospiroindene-2,4′-piperidin]-1-amine 
                 
                   91 
                   (S)-1′-(8-((2-amino-3-chloropyridin-4-yl)thio)pyrido[4,3-d]pyrimidin-5-yl)-6-bromo-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   92 
                   (S)-3-(5-(1-amino-6-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)pyridin-2-yl)-4,5- 
                 
                     
                   dichlorophenol 
                 
                   93 
                   (S)-1-amino-1′-(5-(5-methylthiophen-2-yl)pyrazin-2-yl)-1,3-dihydrospiro[indene-2,4′-piperidin]- 
                 
                     
                   6-ol 
                 
                   94 
                   (S)-1′-(5-(1H-indol-7-yl)pyrazin-2-yl)-5-ethyl-1,3-dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   95 
                   (S)-1′-(5-(cyclohex-1-en-1-yl)pyrazin-2-yl)-5-isopropyl-1,3-dihydrospiro[indene-2,4′-piperidin]- 
                 
                     
                   1-amine 
                 
                   96 
                   (S)-N-(1-amino-1′-(5-(2-(trifluoromethyl)phenyl)pyrimidin-2-yl)-1,3-dihydrospiro[indene-2,4′- 
                 
                     
                   piperidin]-6-yl)methanesulfonamide 
                 
                   97 
                   (S)-1′-(5-((4-(trifluoromethyl)pyrimidin-5-yl)thio)pyrazin-2-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[c]pyridine-6,4′-piperidin]-7-amine 
                 
                   98 
                   (S)-1′-(5-((2-chloropyridin-3-yl)thio)pyrazin-2-yl)-5,7-dihydrospiro[cyclopenta[c]pyridine-6,4′- 
                 
                     
                   piperidin]-5-amine 
                 
                   99 
                   (S)-4-((5-(5-amino-5,7-dihydrospiro[cyclopenta[d]pyrimidine-6,4′-piperidin]-1′-yl)pyrazin-2- 
                 
                     
                   yl)thio)-3-chlorobenzoic acid 
                 
                   100 
                   (S)-1′-(5-((3-(trifluoromethyl)pyrazin-2-yl)thio)pyrazin-2-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-7-amine 
                 
                   101 
                   (S)-1′-(5-((3-chloropyridazin-4-yl)thio)pyrazin-2-yl)-5,7-dihydrospiro[cyclopenta[d]pyrimidine- 
                 
                     
                   6,4′-piperidin]-7-amine 
                 
                   102 
                   (S)-4-((5-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyrazine-6,4′-piperidin]-1′-yl)pyrazin-2- 
                 
                     
                   yl)thio)-3-chlorobenzamide 
                 
                   103 
                   (S)-(1-amino-1′-(5-((3-chloro-2-(methylamino)pyridin-4-yl)thio)pyrazin-2-yl)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-6-yl)dimethylphosphine oxide 
                 
                   104 
                   (S)-1-amino-1′-(6-amino-5-((3-chloro-2-(dimethylamino)pyridin-4-yl)thio)pyrazin-2-yl)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidine]-5-carboxylic acid 
                 
                   105 
                   ethyl (S)-1-amino-1′-(5-((3-chloro-2-(methylamino)pyridin-4-yl)thio)pyrazin-2-yl)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidine]-5-carboxylate 
                 
                   106 
                   (S)-1′-(5-((3-(morpholinomethyl)phenyl)thio)pyrazin-2-yl)-6-(trifluoromethyl)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   107 
                   (S)-6-bromo-5-fluoro-1′-(5-((3-(pentafluoro-16-sulfanyl)phenyl)thio)pyrazin-2-yl)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   108 
                   (S)-N-(3-((5-(1-amino-6-(methylthio)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)pyrazin-2- 
                 
                     
                   yl)thio)phenyl)cyclopropanecarboxamide 
                 
                   109 
                   (S)-6-(6-amino-1-bromo-4H,6H-spiro[cyclopenta[c]thiophene-5,4′-piperidin]-1′-yl)-3-(m-tolyl)- 
                 
                     
                   1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 
                 
                   110 
                   (S)-2-(1-amino-5,6,7-trifluoro-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-(3-ethylphenyl)-3- 
                 
                     
                   methyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one 
                 
                   111 
                   (R)-1′-(3-(3-(tert-butyl)phenyl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-3,4-dihydro-1H- 
                 
                     
                   spiro[naphthalene-2,4′-piperidin]-3-amine 
                 
                   112 
                   (S)-2-(3-amino-1,3-dihydrospiro[cyclopenta[a]naphthalene-2,4′-piperidin]-1′-yl)-5- 
                 
                     
                   (3-isopropylphenyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one 
                 
                   113 
                   (S)-1-amino-1′-(3-(3-chloro-2-morpholinopyridin-4-yl)-4-oxo-4,5-dihydro-1H- 
                 
                     
                   pyrrolo[3,2-c]pyridin-6-yl)-5-fluoro-1,3-dihydrospiro[indene-2,4′-piperidine]-6-carbonitrile 
                 
                   114 
                   (S)-1′-(7-(3-chloro-2-(cyclobutylamino)pyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazin-3-yl)-1,3- 
                 
                     
                   dihydrospiro[cyclopenta[a]naphthalene-2,4′-piperidin]-3-amine 
                 
                   115 
                   (S)-1′-(3-(3-chloro-2-(cyclopropylamino)pyridin-4-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-N6- 
                 
                     
                   methyl-1,3-dihydrospiro[indene-2,4′-piperidine]-1,6-diamine 
                 
                   116 
                   (S)-5-amino-1′-(3-(3-chloro-2-(pyrrolidin-1-yl)pyridin-4-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-2- 
                 
                     
                   fluoro-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidine]-3-carboxamide 
                 
                   117 
                   1-(4-(6-((S)-4-amino-2-chloro-4,6-dihydrospiro[cyclopenta[d]thiazole-5,4′-piperidin]-1′-yl)-1H- 
                 
                     
                   pyrazolo[3,4-b]pyrazin-3-yl)-3-chloropyridin-2-yl)pyrrolidin-3-ol 
                 
                   118 
                   (S)-1′-(3-(3-chloro-2-((cyclopropylmethyl)amino)pyridin-4-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)- 
                 
                     
                   N6,N6-dimethyl-1,3-dihydrospiro[indene-2,4′-piperidine]-1,6-diamine 
                 
                   119 
                   (S)-1′-(3-(2-amino-6-chloropyridin-4-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-2-(tert-butyl)-4,6- 
                 
                     
                   dihydrospiro[cyclopenta[b]thiophene-5,4′-piperidin]-4-amine 
                 
                   120 
                   (S)-2-chloro-1′-(3-(1,3-dihydroisobenzofuran-5-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-4,6- 
                 
                     
                   dihydrospiro[cyclopenta[d]thiazole-5,4′-piperidin]-6-amine 
                 
                   121 
                   (S)-3-chloro-1′-(3-((2-chlorophenyl)thio)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine 
                 
                   122 
                   (S)-1′-(3-(3-chloro-2-(ethylamino)pyridin-4-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-4,6- 
                 
                     
                   dihydrospiro[cyclopenta[b]thiophene-5,4′-piperidin]-4-amine 
                 
                   123 
                   (R)-1′-(7-(methyl(pyridin-4-yl)amino)-5H-pyrrolo[2,3-b]pyrazin-3-yl)-3H- 
                 
                     
                   spiro[furo[2,3-b]pyridine-2,4′-piperidin]-3-amine 
                 
                   124 
                   (R)-1′-(3-((3-chloropyridin-4-yl)amino)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-6,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-5,4′-piperidin]-6-amine 
                 
                   125 
                   (S)-2-methoxy-1′-(3-(1-phenylvinyl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-4,6- 
                 
                     
                   dihydrospiro[cyclopenta[d]thiazole-5,4′-piperidin]-4-amine 
                 
                   126 
                   (R)-1-(3-benzyl-1H-pyrazolo[3,4-b]pyrazin-6-yl)-1′,3′-dihydrospiro[piperidine-4,2′- 
                 
                     
                   pyrrolo[2,3-b]pyridin]-3′-amine 
                 
                   127 
                   (S)-(6-(6-amino-4,6-dihydrospiro[cyclopenta[d]thiazole-5,4′-piperidin]-1′-yl)-1H- 
                 
                     
                   pyrazolo[3,4-b]pyrazin-3-yl)(phenyl)methanone 
                 
                   128 
                   (4S)-1′-(3-(1-phenylethyl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-4,6- 
                 
                     
                   dihydrospiro[cyclopenta[d]thiazole-5,4′-piperidin]-4-amine 
                 
                   129 
                   1-(6-((S)-5-amino-2-methoxy-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-1H- 
                 
                     
                   pyrazolo[3,4-b]pyrazin-3-yl)-1-phenylethan-1-ol 
                 
                   130 
                   (S)-1′-(3-((2,3-dichloropyridin-4-yl)oxy)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine 
                 
                   131 
                   (S)-6-bromo-1′-(3-(5-(3,4-difluorophenyl)-3,4-dihydroquinolin-1(2H)-yl)-1H- 
                 
                     
                   pyrazolo[3,4-b]pyrazin-6-yl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   132 
                   (S)-6-amino-2-(1-amino-6-bromo-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-(4- 
                 
                     
                   cyclopropoxyphenyl)-3-methylpyrimidin-4(3H)-one 
                 
                   133 
                   (S)-N-(1-amino-1′-(4-amino-5-((4-(methylthio)phenyl)thio)-6-oxo-1,6-dihydropyrimidin-2-yl)- 
                 
                     
                   1,3-dihydrospiro[indene-2,4′-piperidin]-6-yl)acetamide 
                 
                   134 
                   (S)-2-(1-amino-6-(methylamino)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-(4- 
                 
                     
                   (benzyloxy)phenyl)-3-methylpyrimidin-4(3H)-one 
                 
                   135 
                   (S)-2-(7-acetyl-1-amino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-(benzo[d][1,3]dioxol- 
                 
                     
                   4-ylthio)pyrimidin-4(3H)-one 
                 
                   136 
                   4-amino-6-((1S)-1-amino-7-(1-hydroxyethyl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3- 
                 
                     
                   (4-(difluoromethoxy)phenyl)-1-methylpyridin-2(1H)-one 
                 
                   137 
                   (S)-1-amino-1′-(4-amino-6-oxo-5-(4-phenoxyphenyl)-1,6-dihydropyridin-2-yl)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidine]-4-carbonitrile 
                 
                   138 
                   (S)-6-(1-amino-4-hydroxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-(4- 
                 
                     
                   cyclohexylphenyl)-1-methylpyridin-2(1H)-one 
                 
                   139 
                   (S)-3-([1,1′-biphenyl]-4-yl)-6-(1-amino-4-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′- 
                 
                     
                   yl)pyridin-2(1H)-one 
                 
                   140 
                   (S)-6-amino-2-(1-amino-6-(2-oxopiperidin-1-yl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3- 
                 
                     
                   methyl-5-(4-(trifluoromethoxy)phenyl)pyrimidin-4(3H)-one 
                 
                   141 
                   (S)-1-(1-amino-1′-(4-amino-5-((4-cyanophenyl)thio)-1-methyl-6-oxo-1,6-dihydropyrimidin-2- 
                 
                     
                   yl)-1,3-dihydrospiro[indene-2,4′-piperidin]-6-yl)urea 
                 
                   142 
                   (S)-4-amino-6-(1-amino-6-chloro-5-fluoro-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-1- 
                 
                     
                   methyl-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)pyridin-2(1H)-one 
                 
                   143 
                   (S)-6-(1-amino-6-(trifluoromethyl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-(4-(2- 
                 
                     
                   methoxyethoxy)phenyl)-1-methylpyridin-2(1H)-one 
                 
                   144 
                   (S)-6-amino-2-(1-amino-6-(piperidine-1-carbonyl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)- 
                 
                     
                   3-methyl-5-(quinolin-8-ylthio)pyrimidin-4(3H)-one 
                 
                   145 
                   (S)-6-amino-2-(1-amino-6-morpholino-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3-methyl- 
                 
                     
                   5-((4-nitrophenyl)thio)pyrimidin-4(3H)-one 
                 
                   146 
                   (S)-6-amino-2-(5-amino-3-nitro-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-3- 
                 
                     
                   methyl-5-(quinolin-8-ylthio)pyrimidin-4(3H)-one 
                 
                   147 
                   (S)-6-(5-amino-3-(4-methylpiperazin-1-yl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′- 
                 
                     
                   piperidin]-1′-yl)-1-methyl-3-(naphthalen-1-ylthio)pyridin-2(1H)-one 
                 
                   148 
                   (S)-2-(1-amino-6-(1H-pyrrol-1-yl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-((2,2- 
                 
                     
                   difluorobenzo[d][1,3]dioxol-4-yl)thio)pyrimidin-4(3H)-one 
                 
                   149 
                   (S)-7-(5-(1-amino-6-(1H-imidazol-1-yl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6- 
                 
                     
                   (hydroxymethyl)-3-methylpyrazin-2-yl)isoindolin-1-one 
                 
                   150 
                   (S)-3-(1-amino-6-(ethylamino)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-(1H-indol-5-yl)- 
                 
                     
                   5-methylpyrazine-2-carboxamide 
                 
                   151 
                   (S)-N-(1-amino-1′-(3-bromo-5-(1H-indol-6-yl)-6-methylpyrazin-2-yl)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-6-yl)cyclopropanecarboxamide 
                 
                   152 
                   (S)-4-(6-amino-5-(1-amino-4-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-3- 
                 
                     
                   methylpyrazin-2-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one 
                 
                   153 
                   (S)-3-(1-amino-5-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-5-methyl-6-(2- 
                 
                     
                   oxoindolin-7-yl)pyrazine-2-carbonitrile 
                 
                   154 
                   (S)-N-(5-(1-amino-7-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-((2- 
                 
                     
                   hydroxyethyl)amino)-3-methylpyrazin-2-yl)benzenesulfonamide 
                 
                   155 
                   (S)-1′-(6-methyl-3-(1H-pyrazol-5-yl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrazin-2-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine 
                 
                   156 
                   (S)-2-(3-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-6-(8- 
                 
                     
                   chlorochroman-7-yl)-5-methylpyrazin-2-yl)propan-2-ol 
                 
                   157 
                   (S)-6-chloro-1′-(5-(7-chloro-2,3-dihydrobenzofuran-6-yl)pyrazin-2-yl)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   158 
                   (S)-4-bromo-1′-(5-(3-(1-methyl-1H-pyrazol-5-yl)phenyl)pyrazin-2-yl)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   159 
                   (S)-1-amino-1′-(6-cyano-5-(1H-indazol-7-yl)pyrazin-2-yl)-5-fluoro-1,3-dihydrospiro[indene-2,4′- 
                 
                     
                   piperidine]-6-carboxamide 
                 
                   160 
                   (S)-1′-(5-(1H-indol-3-yl)-6-iodopyrazin-2-yl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′- 
                 
                     
                   piperidin]-5-amine 
                 
                   161 
                   (R)-6-(5-(7′-amino-7′,8′-dihydro-5′H-spiro[piperidine-4,6′-quinolin]-1-yl)-3-vinylpyrazin-2- 
                 
                     
                   yl)isoindolin-1-one 
                 
                   162 
                   (R)-1-(4-(5-(6-amino-6,7-dihydrospiro[cyclopenta[b]pyridine-5,4′-piperidin]-1′-yl)-3- 
                 
                     
                   ethylpyrazin-2-yl)-3,3-difluoroindolin-1-yl)ethan-1-one 
                 
                   163 
                   (S)-1′-(5-(3-methyl-1H-indazol-6-yl)-6-phenylpyrazin-2-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-5-amine 
                 
                   164 
                   (S)-1′-(5-(1H-benzo[d][1,2,3]triazol-6-yl)-6-cyclopropylpyrazin-2-yl)-6-((tetrahydro-2H-pyran- 
                 
                     
                   4-yl)oxy)-1,3-dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   165 
                   (S)-1-amino-1′-(3-((1-methyl-1H-imidazol-2-yl)thio)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidine]-6-carbonitrile 
                 
                   166 
                   (S)-1′-(3-(1H-benzo[d]imidazol-1-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-6-bromo-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   167 
                   (S)-1-(6-(1-amino-5-chloro-6-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-1H- 
                 
                     
                   pyrazolo[3,4-b]pyrazin-3-yl)-3,4-dihydro-1,5-naphthyridin-2(1H)-one 
                 
                   168 
                   (1-(6-((S)-1-amino-6-(methylthio)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-1H- 
                 
                     
                   pyrazolo[3,4-b]pyrazin-3-yl)-1,2,3,4-tetrahydro-1,5-naphthyridin-4-yl)methanol 
                 
                   169 
                   1-(6-((1S)-1-amino-6-(methylsulfinyl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-1H- 
                 
                     
                   pyrazolo[3,4-b]pyrazin-3-yl)-5-fluoro-1,2,3,4-tetrahydroquinoline-6-carbonitrile 
                 
                   170 
                   (S)-6-chloro-1′-(3-(2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)- 
                 
                     
                   5-methyl-1,3-dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   171 
                   (S)-5-(6-(1-amino-4-methoxy-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-1H-pyrazolo[3,4- 
                 
                     
                   b]pyrazin-3-yl)-N-(2-methoxyethyl)-5,6,7,8-tetrahydro-1,5-naphthyridine-2-carboxamide 
                 
                   172 
                   (S)-1-amino-5-fluoro-1′-(3-(6-(piperazin-1-yl)-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)-1H- 
                 
                     
                   pyrazolo[3,4-b]pyrazin-6-yl)-1,3-dihydrospiro[indene-2,4′-piperidine]-6-carbonitrile 
                 
                   173 
                   (S)-2-(1-(6-(1-amino-6-(methylthio)-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-1H- 
                 
                     
                   pyrazolo[3,4-b]pyrazin-3-yl)-1,2,3,4-tetrahydroquinolin-5-yl)thiazole-4-carboxylic acid 
                 
                   174 
                   (S)-1′-(6-(aminomethyl)-5-(2,3-dichloropyridin-4-yl)pyrazin-2-yl)-6-(1H-imidazol-1-yl)-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   175 
                   (1S)-1-amino-1′-(5-(2,3-dichloropyridin-4-yl)-3-(2-(hydroxymethyl)pyrrolidine-1-carbonyl)-6- 
                 
                     
                   methylpyrazin-2-yl)-N,N-dimethyl-1,3-dihydrospiro[indene-2,4′-piperidine]-6-carboxamide 
                 
                   176 
                   (S)-1′-(8-(2-amino-3-chloropyridin-4-yl)-7-methylimidazo[1,2-c]pyrimidin-5-yl)-5-fluoro-1,3- 
                 
                     
                   dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   177 
                   (S)-1′-(5-(1-methyl-1H-indol-2-yl)pyrazin-2-yl)-1,3-dihydrospiro[indene-2,4′-piperidin]-3,3-d2- 
                 
                     
                   1-amine 
                 
                   178 
                   (S)-1-(6-(5-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidin]-1′-yl)-1H- 
                 
                     
                   pyrazolo[3,4-b]pyrazin-3-yl)-1,2,3,4-tetrahydro-6H-pyrido[1,2-a]pyrimidin-6-one 
                 
                   179 
                   (S)-1′-(3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[c]pyridine-6,4′-piperidin]-5-amine 
                 
                   180 
                   (3-((S)-1-amino-6-fluoro-1,3-dihydrospiro[indene-2,4′-piperidin]-1′-yl)-6-((R)-1- 
                 
                     
                   methylisoindolin-2-yl)pyrazin-2-yl)methanol 
                 
                   181 
                   (S)-1′-(3-(6,7-dihydropyrazolo[1,5-a]pyrimidin-4(5H)-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-5,7- 
                 
                     
                   dihydrospiro[cyclopenta[c]pyridine-6,4′-piperidin]-5,5-d2-7-amine 
                 
                   182 
                   (S)-4-(difluoromethyl)-1′-(5-methyl-6-((R)-2-methyl-3,4-dihydro-1,5-naphthyridin-1(2H)- 
                 
                     
                   yl)pyridin-3-yl)-1,3-dihydrospiro[indene-2,4′-piperidin]-1-amine 
                 
                   183 
                   (S)-1′-(8-(2-chloro-3-(isopropyl(methyl)amino)phenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-yl)- 
                 
                     
                   2,3,6,8-tetrahydrospiro[indeno[5,6-b][1,4]dioxine-7,4′-piperidin]-6-amine 
                 
                   184 
                   (S)-1-(5-amino-1′-(8-((5-chloro-1-methylindolin-6-yl)thio)imidazo[1,5-a]pyridin-5-yl)-2,3,5,7- 
                 
                     
                   tetrahydro-1H-spiro[cyclopenta[b]pyrrolo[3,2-e]pyridine-6,4′-piperidin]-1-yl)ethan-1-one 
                 
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         340 . A pharmaceutical composition comprising at least one compound or a pharmaceutically acceptable salt thereof as defined in any one of  claims 1 - 339  and at least one pharmaceutically acceptable excipient. 
     
     
         341 . The pharmaceutical composition of  claim 340 , wherein, the compound in a weight ratio to the said excipient within the range from about 0.0001 to about 10. 
     
     
         342 . A combination pharmaceutical product comprising the compound or a pharmaceutically acceptable salt thereof of any of  claims 1 - 339 , together with one or more other therapeutically active agents. 
     
     
         343 . Use of the compound or a pharmaceutically acceptable salt thereof of any one of  claim 1 - 339 , the pharmaceutical composition of  claim 340  or  341 , or the combination pharmaceutical product of  claim 342  for the preparation of a medicament. 
     
     
         344 . The use of  claim 343 , wherein the medicament is used for the treatment or prevention of cancer, cancer metastasis, cardiovascular disease, an immunological disorder or an ocular disorder. 
     
     
         345 . Use, in the manufacture of a medicament for use as an inhibitor of SHP2, of at least one compound or a pharmaceutically acceptable salt thereof any one of  claims 1 - 339 , the pharmaceutical composition of  claim 340  or  341 , or the combination pharmaceutical product of  claim 342 . 
     
     
         346 . Use of the compound or a pharmaceutically acceptable salt thereof of any one of  claims 1 - 339 , the pharmaceutical composition of  claim 340  or  341 , or the combination pharmaceutical product of  claim 342  for the preparation of a medicament in the treatment of diseases or conditions mediated by the activity of SHP2. 
     
     
         347 . The use of  claim 346 , wherein the diseases or conditions mediated by the activity of SHP2 is cancer. 
     
     
         348 . The use of  claim 346 , wherein the diseases or conditions mediated by the activity of SHP2 is selected from Noonan syndrome, leopard syndrome, juvenile myelomonocytic leukemias, liver cancer, neuroblastoma, melanoma, squamous-cell carcinoma of the head and neck, acute myeloid leukemia, breast cancer, esophageal cancer, lung cancer, colon cancer, head cancer, gastric carcinoma, neuroblastoma, anaplastic large-cell lymphoma and glioblastoma. 
     
     
         349 . A method for preventing or treating a disease, lessening a disease symptoms, delaying the progression or onset of a disease, comprising administering to the patient in need thereof a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof of any one of  claims 1 - 339 , the pharmaceutical composition of  claims 340  or  341 , or the combination pharmaceutical product of  claim 342 , wherein the disease is cancer, cancer metastasis, cardiovascular disease, an immunological disorder or an ocular disorder. 
     
     
         350 . A method for inhibiting the activity of SHP2 level, comprising administering to the patient in need thereof a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof of any one of  claims 1 - 339 , or the pharmaceutical composition of  claim 340  or  341 , or the combination pharmaceutical product of  claim 342 . 
     
     
         351 . A method for preventing or treating a disease, lessening a disease symptoms, delaying the progression or onset of a disease, comprising administering to the patient in need thereof a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof of any one of  claims 1 - 339 , the pharmaceutical composition of  claim 340  or  341 , or the combination pharmaceutical product of  claim 342 , wherein the disease is mediated by the activity of SHP2. 
     
     
         352 . The method of  claim 351 , wherein the disease mediated by the activity of SHP2 is cancer. 
     
     
         353 . The method of  claim 351 , wherein the disease mediated by the activity of SHP2 is selected from Noonan syndrome, leopard syndrome, juvenile myelomonocytic leukemias, liver cancer, neuroblastoma, melanoma, squamous-cell carcinoma of the head and neck, acute myeloid leukemia, breast cancer, esophageal cancer, lung cancer, colon cancer, head cancer, gastric carcinoma, neuroblastoma, anaplastic large-cell lymphoma and glioblastoma. 
     
     
         354 . The compound or the pharmaceutically acceptable salt thereof of any one of  claims 1 - 339 , the pharmaceutical composition of  claim 340  or  341 , or the combination pharmaceutical product of  claim 342  for use in preventing or treating a disease, lessening a disease symptom, delaying the progression or onset of a disease, wherein the disease is cancer, cancer metastasis, cardiovascular disease, an immunological disorder or an ocular disorder. 
     
     
         355 . The compound or the pharmaceutically acceptable slat thereof any one of  claims 1 - 339 , the pharmaceutical composition of  claim 340  or  341 , or the combination pharmaceutical product of  claim 339 , for use in inhibiting the activity of SHP2. 
     
     
         356 . The compound or the pharmaceutically acceptable salt thereof of any one of  claims 1 - 339 , the pharmaceutical composition of  claim 340  or  341 , or the combination pharmaceutical product of  claim 339  for use in preventing or treating a disease, lessening a disease symptom, delaying the progression or onset of a disease, wherein the disease is mediated by the activity of SHP2. 
     
     
         357 . The compound or the pharmaceutically acceptable salt thereof, the pharmaceutical composition, or the combination pharmaceutical product of  claim 356 , wherein the disease mediated by the activity of SHP2 is cancer. 
     
     
         358 . The compound or the pharmaceutically acceptable salt thereof, the pharmaceutical composition, or the combination pharmaceutical product of  claim 356 , wherein the disease mediated by the activity of SHP2 is selected from Noonan syndrome, leopard syndrome, juvenile myelomonocytic leukemias, liver cancer, neuroblastoma, melanoma, squamous-cell carcinoma of the head and neck, acute myeloid leukemia, breast cancer, esophageal cancer, lung cancer, colon cancer, head cancer, gastric carcinoma, neuroblastoma, anaplastic large-cell lymphoma and glioblastoma.