Substituted 6,5-fused bicyclic heteroaryl compounds

Abstract

The present invention relates to substituted 6,5-fused bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof.

1 .- 19 . (canceled) 
     
     
         20 . A method of treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (Ib) or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein
 X 2  is N or CH; 
 X 3  is CR 8 ; 
 X 4  is C; 
 Y 1  is CH; 
 Y 3  is CR 11 ; 
 R 6  is phenyl or a 5 to 6-membered heteroaryl selected from the group consisting of pyridinyl, pyrazolyl, pyrimidinyl, and furyl, wherein the phenyl and 5 to 6-membered heteroaryl are substituted with one or more -Q 2 -T 2 , in which Q 2  is a bond, and T 2  is unsubstituted 4 to 7-membered heterocycloalkyl; 
 R 7  is C 1 -C 6  alkyl or cyclopentyl; 
 each of R 8  independently is H or methyl or ethyl; and 
 R 11  is H. 
 
       
     
     
         21 . The method of  claim 20 , wherein R 6  is pyridinyl optionally substituted with one or more -Q 2 -T 2 . 
     
     
         22 . The method of  claim 21 , wherein X 2  is CH. 
     
     
         23 . The method of  claim 22 , wherein T 2  is azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, isoxazolidinyl, triazolidinyl, tetrahyrofuranyl, piperidinyl, 1,2,3,6-tetrahydropyridinyl, piperazinyl, tetrahydro-2H-pyranyl, 3,6-dihydro-2H-pyranyl, or morpholinyl. 
     
     
         24 . The method of  claim 23 , wherein T 2  is piperazinyl. 
     
     
         25 . The method of  claim 24 , wherein R 7  is methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, s-pentyl, or n-hexyl. 
     
     
         26 . The method of  claim 25 , wherein R 7  is s-butyl. 
     
     
         27 . The method of  claim 26 , wherein R 11  is H. 
     
     
         28 . The method of  claim 27 , wherein R 8  is methyl. 
     
     
         29 . The method of  claim 28 , wherein the compound has R configuration. 
     
     
         30 . The method of  claim 28 , wherein the compound has S configuration. 
     
     
         31 . The method of  claim 20 , wherein the cancer overexpresses EZH2 or other PRC2 subunits, contains loss-of-function mutations in H3-K27 demethylases, or overexpresses accessory proteins. 
     
     
         32 . The method of  claim 20 , wherein the cancer is leukemia or lymphoma. 
     
     
         33 . The method of  claim 32 , wherein the leukemia is selected from the group consisting of chronic lymphocytic leukemia, chronic myelogenous leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, hairy cell leukemia, chronic myelogenous leukemia, and acute myeloid leukemia. 
     
     
         34 . The method of  claim 20 , wherein the cancer is lymphoma. 
     
     
         35 . The method of  claim 34 , wherein the lymphoma is selected from the group consisting of B-cell lymphoma, diffuse large B-cell lymphoma, germinal center B cell-like lymphoma, cutaneous T-cell lymphoma, AIDS-related lymphoma, nervous system lymphoma, follicular lymphoma, and non-Hodgkin lymphoma. 
     
     
         36 . The method of  claim 35 , wherein the lymphoma is B-cell lymphoma. 
     
     
         37 . The method of  claim 35 , wherein the lymphoma is diffuse large B-cell lymphoma. 
     
     
         38 . The method of  claim 35 , wherein the lymphoma is follicular lymphoma. 
     
     
         39 . The method of  claim 35 , wherein the lymphoma is non-Hodgkin lymphoma.