US2017174679A1PendingUtilityA1
Heterocyclic compounds as immunomodulators
Est. expiryDec 22, 2035(~9.4 yrs left)· nominal 20-yr term from priority
A61P 35/04A61P 9/10A61P 31/12A61P 3/00A61P 31/00A61P 35/00A61K 31/519A61K 31/4375C07D 471/04C07D 215/40A61K 31/4985A61K 31/47A61P 11/06C07D 401/06A61P 35/02A61P 31/04A61P 31/10A61P 31/14A61P 31/16A61P 31/18A61P 31/20A61P 31/22A61P 33/00A61P 33/02A61P 33/06
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Claims
Abstract
Disclosed are compounds of Formula (I′), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of Formula (I′):
or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein:
X 1 is N or CR 1 ;
X 2 is N or CR 2 ;
X 3 is N or CR 3 ;
X 4 is N or CR 4 ;
X 5 is N or CR 5 ;
X 6 is N or CR 6
wherein X 1 , X 2 and X 3 are not all simultaneously N;
wherein X 4 , X 5 and X 6 are not all simultaneously N;
X 7 is N or CR 8a :
X 8 is N or CR 8b ;
X 9 is N or CR 8c ;
Cy is C 6-10 aryl, C 3-10 cycloalkyl, 5- to 14-membered heteroaryl, or 4- to 10-membered heterocycloalkyl, each of which is optionally substituted with 1 to 4 independently selected R 9 substituents;
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 are each independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO 2 , OR a , SR a , NHOR a , C(O)R a , C(O)NR a R a , C(O)OR a , OC(O)R a , OC(O)NR a R a , NHR a , NR a R a , NR a C(O)R a , NR a C(O)OR a , NR a C(O)NR a R a , C(═NR a )R a , C(═NR a )NR a R a , NR a C(═NR a )NR a R a , NR a S(O)R a , NR a S(O) 2 R a , NR a S(O) 2 NR a R a , S(O)R a , S(O)NR a R a , S(O) 2 R a , and S(O) 2 NR a R a , wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 are each optionally substituted with 1, 2, 3, or 4 R b substituents;
R 7 is halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, OR 11 , SR 11 , NH 2 , NHR 11 , NR 11 R 11 , NHOR 11 , C(O)R 11 , C(O)NR 11 R 11 , C(O)OR 11 , OC(O)R 11 , OC(O)NR 11 R 11 , NR 11 C(O)R 11 , NR 11 C(O)OR 11 , NR 11 C(O)NR 11 R 11 , C(═NR 11 )R 11 , C(═NR 11 )NR 11 R 11 , NR 11 C(═NR 11 )NR 11 R 11 , NR 11 S(O)R 11 , NR 11 S(O) 2 R 11 , NR 11 S(O) 2 NR 11 R 11 S(O)R 11 , S(O)NR 11 R 11 , S(O) 2 R 11 , and S(O) 2 NR 11 R 11 , wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R 9 and R 11 are each optionally substituted with 1, 2 or 3 R b substituents;
each R 11 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R 11 are each optionally substituted with 1, 2 or 3 independently selected R b substituents;
R 8a , R 8b and R 8c are each independently selected from H, C 1-4 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkyl-, C 6-10 aryl, C 6-10 aryl-C 1-4 alkyl-, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, C 2-4 alkenyl, C 2-4 alkynyl, halo, CN, OR 10 , C 1-4 haloalkyl, C 1-4 haloalkoxy, NH 2 , —NHR 10 , —NR 10 R 10 , NHOR 10 , C(O)R 10 , C(O)NR 10 R 10 , C(O)OR 10 , OC(O)R 10 , OC(O)NR 10 R 10 , NR 10 C(O)R 10 , NR 10 C(O)OR 10 NR 10 C(O)NR 10 R 10 , C(═NR 10 )R 10 , C(═NR 10 )NR 10 R 10 , NR 10 C(═NR 10 )NR 10 OR 10 , NR 10 S(O)R 10 , NR 10 S(O) 2 R 10 , NR 10 S(O) 2 NR 10 R 10 , S(O)R 10 S(O)NR 10 R 10 , S(O) 2 R 10 , and S(O) 2 NR 10 R 10 , wherein each R 10 is independently selected from H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkyl-, C 6-10 aryl, C 6-10 aryl-C 1-4 alkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein the C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkyl-, C 6-10 aryl, C 6-10 aryl-C 1-4 alkyl-, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R 8a , R 8b , R 8c and R 10 are each optionally substituted with 1, 2 or 3 independently selected R d substituents;
or two adjacent R 9 substituents together with the atoms to which they are attached, form a fused phenyl ring, a fused 5- to 7-membered heterocycloalkyl ring, a fused 5- or 6-membered heteroaryl ring or a fused C 3-10 cycloalkyl ring, wherein the fused 5- to 7-membered heterocycloalkyl ring and fused 5- or 6-membered heteroaryl ring each have 1-4 heteroatoms as ring members selected from N, O and S and wherein the fused phenyl ring, fused 5- to 7-membered heterocycloalkyl ring, fused 5- or 6-membered heteroaryl ring and fused C 3-10 cycloalkyl ring are each optionally substituted with 1, 2 or 3 independently selected R b substituents;
each R a is independently selected from H, CN, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R a are each optionally substituted with 1, 2, 3, 4, or 5 R d substituents;
each R d is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NH 2 , NHOR e , OR e , SR e , C(O)R e , C(O)NR e R e , C(O)OR e , OC(O)R e , OC(O)NR e R e , NHR e , NR e R e , NR e C(O)R e , NR e C(O)NR e R e , NR e C(O)OR e , C(═NR e )NR e R e , NR e C(═NR e )NR e R e , NR e C(═NOH)NR e R e , NR e C(═NCN)NR e R e , S(O)R e , S(O)NR e R e , S(O) 2 R e , NR e S(O) 2 R e , NR e S(O) 2 NR e R e , and S(O) 2 NR e R e , wherein the C 1-6 alkyl, C 1-6 haloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R d are each optionally substituted with 1-3 independently selected R h substituents;
each R b substituent is independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, OH, NH 2 , NO 2 , NHOR c , OR c , SR c , C(O)R c , C(O)NR c R c , C(O)OR c , OC(O)R c , OC(O)NR c R c , C(═NR c )NR c R c , NR c C(═NR c )NR c R c , NHR c , NR c R c , NR c C(O)R c , NR c C(O)OR c , NR c C(O)NR c R c , NR c S(O)R c , NR c S(O) 2 R c , NR c S(O) 2 NR c R c , S(O)R c , S(O)NR c R c , S(O) 2 R c or S(O) 2 NR c R c ; wherein the C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R b are each further optionally substituted with 1-3 independently selected R d substituents;
each R c is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R c are each optionally substituted with 1, 2, 3, 4, or 5 R f substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 iaryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, halo, CN, NHOR g , OR g , SR g , C(O)R g , C(O)NR g R g , C(O)OR g , OC(O)R g , OC(O)NR g R g , NHR g , NR g R g , NR g C(O)R g , NR g C(O)NR g R g , NR g C(O)OR g , C(═NR g )NR g R g , NR g C(═NR g )NR g R g , S(O)R g , S(O)NR g R g , S(O) 2 R, NR g S(O) 2 R g , NR g S(O) 2 NR g R g , and S(O) 2 NR g R g ; wherein the C 1-4 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R f are each optionally substituted with 1, 2, 3, 4, or 5 R n substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, halo, CN, R o , NHOR o , OR o , SR o , C(O)R o , C(O)NR o R o , C(O)OR o , OC(O)R o , OC(O)NR o R o , NHR o , NR o R o , NR o C(O)R o , NR o C(O)NR o R o , NR o C(O)OR o , C(═NR)NR o R o , NR o C(═NR)NR o R o , S(O)R o , S(O)NR o R o , S(O) 2 R o , NR o S(O) 2 R o , NR o S(O) 2 NR o R o , and S(O) 2 NR o R o ;
each R g is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R g are each optionally substituted with 1-3 R p substituents independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-(5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, halo, CN, NHOR r , OR r , SR r , C(O)R r , C(O)NR r R r , C(O)OR r , OC(O)R r , OC(O)NR r R r , NHR r , NR r R r , NR r C(O)R r , NR r C(O)NR r R r , NR r C(O)OR r , C(═NR r )NR r R r , NR r C(═NR r )NR r R r , NR r C(═NOH)NR r R r , NR r C(═NCN)NR r R r , S(O)R r , S(O)NR r R r , S(O) 2 R r , NR r S(O) 2 R r , NR r S(O) 2 NR r R r and S(O) 2 NR r R r , wherein the C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R p is optionally substituted with 1, 2 or 3 R q substituents;
or any two R a substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 R h substituents independently selected from C 1-6 alkyl, C 3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-6 membered heteroaryl)-C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-C 1-4 alkyl-, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo, CN, OR i , SR i , NHOR i , C(O)R i , C(O)NR i R i , C(O)OR i , OC(O)R i , OC(O)NR i R i , NHR i , NR i R i , NR i C(O)R i , NR i C(O)NR i R i , NR i C(O)OR i , C(═NR i )NR i R i , NR i C(═NR i )NR i R i , S(O)R i , S(O)NR i R i , S(O) 2 R i , NR i S(O) 2 R i , NR i S(O) 2 NR i R i , and S(O) 2 NR i R i , wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-6 membered heteroaryl)-C 1-4 alkyl-, and (4-7 membered heterocycloalkyl)-C 1-4 alkyl- of R h are each further optionally substituted by 1, 2, or 3 R j substituents independently selected from C 3-6 cycloalkyl, C 6-10 aryl, 5 or 6-membered heteroaryl, 4-7 membered heterocycloalkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo, C 1-4 alkyl, C 1-4 haloalkyl, CN, NHOR k , OR k , SR k , C(O)R k , C(O)NR k R k , C(O)OR k , OC(O)R k , OC(O)NR k R k , NHR k , NR k R k , NR k C(O)R k , NR k C(O)NR k R k , NR k C(O)OR k , C(═NR k )NR k R k , NR k C(═NR k )NR k R k , S(O)R k , S(O)NR k R k , S(O) 2 R k , NR k S(O) 2 R k , NR k S(O) 2 NR k R k , and S(O) 2 NR k R k , wherein the C 1-4 alkyl, C 3-6 cycloalkyl, C 6-10 aryl, 5- or 6-membered heteroaryl, 4-6 membered heterocycloalkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, and C 1-4 haloalkoxy of R j are each optionally substituted with 1, 2 or 3 independently selected R q substituents; or two R h groups attached to the same carbon atom of the 4- to 10-membered heterocycloalkyl taken together with the carbon atom to which they are attached form a C 3-6 cycloalkyl or 4- to 6-membered heterocycloalkyl having 1-2 heteroatoms as ring members selected from O, N or S;
or any two R c substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;
or any two R e substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;
or any two R g substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;
or any two R i substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;
or any two R k substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;
or any two R o substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents; and
each R e , R i , R k , R o or R r is independently selected from H, C 1-4 alkyl, C 3-6 cycloalkyl, C 6-10 aryl, 5 or 6-membered heteroaryl, 4-7 membered heterocycloalkyl, C 1-4 haloalkyl, C 2-4 alkenyl, and C 2-4 alkynyl, wherein the C 1-4 alkyl, C 3-6 cycloalkyl, C 6-10 aryl, 5 or 6-membered heteroaryl, 4-7 membered heterocycloalkyl, C 2-4 alkenyl, and C 2-4 alkynyl of R e , R i , R k , R o or R p are each optionally substituted with 1, 2 or 3 R q substituents;
each R q is independently selected from OH, CN, —COOH, NH 2 , halo, C 1-6 haloalkyl, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, phenyl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C 3-6 cycloalkyl, NHR 12 , NR 12 R 12 , and C 1-4 haloalkoxy, wherein the C 1-6 alkyl, phenyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl of R q are each optionally substituted with halo, OH, CN, —COOH, NH 2 , C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, phenyl, C 3-10 cycloalkyl, 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl and each R 12 is independently C 1-6 alkyl;
provided that R 7 is other than NH 2 , when X 8 is CR 8b and X 7 and X 9 are each N; and
the compound is other than (1R,5S,6R)-5-(2,6-difluoro-3-((2-methoxypyrido[3,4-b]pyrazin-5-yl)amino)phenyl)-5-(fluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine or (1S,5R,6S)-5-(2,6-difluoro-3-((2-methoxypyrido[3,4-b]pyrazin-5-yl)amino)phenyl)-5-(fluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine.
2 . The compound claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein:
X 1 is N or CR 1 ; X 2 is N or CR 2 ; X 3 is N or CR 3 ; X 4 is N or CR 4 ; X 5 is N or CR 5 ; X 6 is N or CR 6 wherein X 1 , X 2 and X 3 are not all simultaneously N; wherein X 4 , X 5 and X 6 are not all simultaneously N; X 7 is N or CR 8a ; X 8 is N or CR 8b ; X 9 is N or CR 8c ; Cy is C 6-10 aryl, C 3-10 cycloalkyl, 5- to 14-membered heteroaryl, or 4- to 10-membered heterocycloalkyl, each of which is optionally substituted with 1 to 4 independently selected R 9 substituents; R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 are each independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO 2 , OR a , SR a , NHOR a , C(O)R a , C(O)NR a R a , C(O)OR a , OC(O)R a , OC(O)NR a R a , NHR a , NR a R a , NR a C(O)R a , NR a C(O)OR a , NR a C(O)NR a R a , C(═NR a )R a , C(═NR a )NR a R a , NR a C(═NR a )NR a R a , NR a S(O)R a , NR a S(O) 2 R a , NR a S(O) 2 NR a R a , S(O)R a , S(O)NR a R a , S(O) 2 R a , and S(O) 2 NR a R a , wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 are each optionally substituted with 1, 2, 3, or 4 R b substituents; R 7 is C 1-4 alkyl, halo, CN, OH, cyclopropyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, NH 2 , —NH—C 1-4 alkyl, —N(C 1-4 alkyl) 2 , OR 11 , NHOR 11 , C(O)R 11 , C(O)NR 11 R 11 , C(O)OR 11 , OC(O)R 11 , OC(O)NR 11 R 11 , NR 11 C(O)R 11 , NR 11 C(O)OR 11 , NR 11 C(O)NR 11 R 11 , C(═NR 11 )R 11 , C(═NR 11 )NR 11 R 11 , NR 11 C(═NR 11 )NR 11 R 11 , NR 11 S(O)R 11 , NR 11 S(O) 2 R 11 , NR 11 S(O) 2 NR 11 R 11 , S(O)R 11 , S(O)NR 11 R 11 , S(O) 2 R 11 , and S(O) 2 NR 11 R 11 , wherein the C 1-4 alkyl, cyclopropyl, C 2-4 alkynyl and C 1-4 alkoxy of R 7 are each optionally substituted with 1 or 2 halo, OH, CN or OCH 3 substituents and each R 11 is independently selected from H and C 1-4 alkyl optionally substituted with 1 or 2 halo, OH, CN or OCH 3 ; R 8a , R 8b and R 8c are each independently selected from H, C 1-4 alkyl, C 3-6 cycloalkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo, CN, OH, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, NH 2 , —NH—C 1-4 alkyl, —N(C 1-4 alkyl) 2 , OR 10 , NHOR 10 , C(O)R 10 , C(O)NR 10 R 10 , C(O)OR 10 , OC(O)R 10 , OC(O)NR 10 R 10 , NR 10 C(O)R 10 , NR 10 C(O)OR 10 , NR 10 C(O)NR 10 R 10 , C(═NR 10 )R 10 , C(═NR 10 )NR 10 R 10 , NR 10 C(═NR 10 )NR 10 R 10 , NR 10 S(O)R 10 , NR 10 S(O) 2 R 10 , NR 10 S(O) 2 NR 10 R 10 , S(O)R 10 , S(O)NR 10 R 10 , S(O) 2 R 10 , and S(O) 2 NR 10 R 10 , wherein each R 10 is independently H or C 1-4 alkyl optionally substituted with 1 or 2 groups independently selected from halo, OH, CN and C 1-4 alkoxy and wherein the C 1-4 alkyl, C 3-6 cycloalkyl, C 2-4 alkenyl and C 2-4 alkynyl of R 8 are each optionally substituted with 1 or 2 substituents independently selected from halo, OH, CN, C 1-4 alkyl and C 1-4 alkoxy; or two adjacent R 9 substituents together with the carbon atoms to which they are attached, form a fused phenyl ring, a fused 5- to 7-membered heterocycloalkyl ring, a fused 5- or 6-membered heteroaryl ring or a fused C 3-10 cycloalkyl ring, wherein the fused 5- to 7-membered heterocycloalkyl ring and fused 5- or 6-membered heteroaryl ring each have 1-4 heteroatoms as ring members selected from N, O and S and wherein the fused phenyl ring, fused 5- to 7-membered heterocycloalkyl ring, fused 5- or 6-membered heteroaryl ring and fused C 3-10 cycloalkyl ring are each optionally substituted with 1 or 2 independently selected R b substituents; each R a is independently selected from H, CN, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R a are each optionally substituted with 1, 2, 3, 4, or 5 R d substituents; each R d is independently selected from C 1-4 alkyl, C 1-4 haloalkyl, halo, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, phenyl, 5- or 6-membered heteroaryl, CN, NH 2 , NHOR e , OR e , SR e , C(O)R e , C(O)NR e R e , C(O)OR e , OC(O)R e , OC(O)NR e R e , NHR e , NR e R e , NR e C(O)R e , NR e C(O)NR e R e , NR e C(O)OR e , C(═NR e )NR e R e , NR e C(═NR e )NR e R e , S(O)R e , S(O)NR e R e , S(O) 2 R e , NR e S(O) 2 R e , NR e S(O) 2 NR e R e , and S(O) 2 NR e R e , wherein the C 1-4 alkyl, C 3-10 cycloalkyl, phenyl, 5- or 6-membered heteroaryl and 4-10 membered heterocycloalkyl of R d are each further optionally substituted with 1-3 independently selected R q substituents; each R b substituent is independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, OH, NH 2 , NO 2 , NHOR c , OR c , SR c , C(O)R c , C(O)NR c R c , C(O)OR c , OC(O)R c , OC(O)NR c R c , C(═NR c )NR c R c , NR c C(═NR c )NR c R c , NHR c , NR c R c , NR c C(O)R c , NR c C(O)OR c , NR c C(O)NR c R c , NR c S(O)R c , NR c S(O) 2 R c , NR c S(O) 2 NR c R c , S(O)R c , S(O)NR c R c , S(O) 2 R c or S(O) 2 NR c R c ; wherein the C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R b are each further optionally substituted with 1-3 independently selected R d substituents; each R c is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R c are each optionally substituted with 1, 2, 3, 4, or 5 R f substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, halo, CN, NHOR g , OR g , SR g , C(O)R g , C(O)NR g R g , C(O)OR g , OC(O)R g , OC(O)NR g R g , NHR g , NR g R g , NR g C(O)R g , NR g C(O)NR g R g , NR g C(O)OR g , C(═NR g )NR g R g , NR g C(═NR g )NR g R g , S(O)R g , S(O)NR g R g , S(O) 2 R g , NR g S(O) 2 R g , NR g S(O) 2 NR g R g , and S(O) 2 NR g R g ; wherein the C 1-4 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R f are each optionally substituted with 1, 2, 3, 4, or 5 R n substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, halo, CN, R o , NHOR o , OR o , SR o , C(O)R o , C(O)NR o R o , C(O)OR o , OC(O)R o , OC(O)NR o R o , NHR o , NR o R o , NR o C(O)R o , NR o C(O)NR o R o , NR o C(O)OR o , C(═NR o )NR o R o , NR o C(═NR o )NR o R o , S(O)R o , S(O)NR o R o , S(O) 2 R o , NR o S(O) 2 R o , NR o S(O) 2 NR o R o , and S(O) 2 NR o R o ; each R g is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R g are each optionally substituted with 1-3 independently selected R p substituents; or any two R a substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 R h substituents independently selected from C 1-6 alkyl, C 3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-6 membered heteroaryl)-C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-C 1-4 alkyl-, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo, CN, OR i , SR i , NHOR i , C(O)R i , C(O)NR i R i , C(O)OR i , OC(O)R i , OC(O)NR i R i , NHR i , NR i R i , NR i C(O)R i , NR i C(O)NR i R i , NR i C(O)OR i , C(═NR i )NR i R i , NR i C(═NR i )NR i R i , S(O)R i , S(O)NR i R i , S(O) 2 R i , NR i S(O) 2 R i , NR i S(O) 2 NR i R i , and S(O) 2 NR i R i , wherein the C 1-6 alkyl, C 3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-6 membered heteroaryl)-C 1-4 alkyl-, and (4-7 membered heterocycloalkyl)-C 1-4 alkyl- of R h are each further optionally substituted by 1, 2, or 3 R j substituents independently selected from C 3-6 cycloalkyl, C 6-10 aryl, 5 or 6-membered heteroaryl, C 2-4 alkenyl, C 2-4 alkynyl, halo, C 1-4 alkyl, C 1-4 haloalkyl, CN, NHOR k , OR k , SR k , C(O)R k , C(O)NR k R k , C(O)OR k , OC(O)R k , OC(O)NR k R k , NHR k , NR k R k , NR k C(O)R k , NR k C(O)NR k R k , NR k C(O)OR k , C(═NR k )NR k R k , NR k C(═NR k )NR k R k , S(O)R k , S(O)NR k R k , S(O) 2 R k , NR k S(O) 2 R k , NR k S(O) 2 NR k R k , and S(O) 2 NR k R k ; or two R h groups attached to the same carbon atom of the 4- to 10-membered heterocycloalkyl taken together with the carbon atom to which they are attached form a C 3-6 cycloalkyl or 4- to 6-membered heterocycloalkyl having 1-2 heteroatoms as ring members selected from O, N or S; or any two R c substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents; or any two R e substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents; or any two R g substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents; or any two R i substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents; or any two R k substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents; or any two R o substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents; and each R e , R i , R k , R o or R p is independently selected from H, C 1-4 alkyl, C 3-6 cycloalkyl, C 6-10 aryl, 5 or 6-membered heteroaryl, C 1-4 haloalkyl, C 2-4 alkenyl, and C 2-4 alkynyl, wherein the C 1-4 alkyl, C 3-6 cycloalkyl, C 6-10 aryl, 5 or 6-membered heteroaryl, C 2-4 alkenyl, and C 2-4 alkynyl of R e , R i , R k , R o or R p are each optionally substituted with 1, 2 or 3 R q substituents; each R q is independently selected from OH, CN, —COOH, NH 2 , halo, C 1-6 haloalkyl, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, phenyl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C 3-6 cycloalkyl, NHR 12 , NR 12 R 12 , and C 1-4 haloalkoxy, wherein the C 1-6 alkyl, phenyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl of R q are each optionally substituted with halo, OH, CN, —COOH, NH 2 , C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, phenyl, C 3-10 cycloalkyl and 4-6 membered heterocycloalkyl and each R 12 is independently C 1-6 alkyl; provided that R 7 is other than NH 2 , when X 8 is CR 8b and X 7 and X 9 are each N; and the compound is other than (1R,5S,6R)-5-(2,6-difluoro-3-((2-methoxypyrido[3,4-b]pyrazin-5-yl)amino)phenyl)-5-(fluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine or (1S,5R,6S)-5-(2,6-difluoro-3-((2-methoxypyrido[3,4-b]pyrazin-5-yl)amino)phenyl)-5-(fluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine.
3 . The compound of claim 1 or 2 , having Formula (I):
or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein:
X 1 is N or CR 1 ;
X 2 is N or CR 2 ;
X 3 is N or CR 3 ;
X 4 is N or CR 4 ;
X 5 is N or CR 5 ;
X 6 is N or CR 6
wherein X 1 , X 2 and X 3 are not all simultaneously N;
wherein X 4 , X 5 and X 6 are not all simultaneously N;
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 are each independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO 2 , OR a , SR a , NHOR a , C(O)R a , C(O)NR a R a , C(O)OR a , OC(O)R a , OC(O)NR a R a , NHR a , NR a R a , NR a C(O)R a , NR a C(O)OR a , NR a C(O)NR a R a , C(═NR a )R a , C(═NR a )NR a R a , NR a C(═NR a )NR a R a , NR a S(O)R a , NR a S(O) 2 R a , NR a S(O) 2 NR a R a , S(O)R a , S(O)NR a R a , S(O) 2 R a , and S(O) 2 NR a R a , wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 are each optionally substituted with 1, 2, 3, or 4 R b substituents;
R 7 is C 1-4 alkyl, halo, CN, OH, cyclopropyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, NH 2 , —NH—C 1-4 alkyl, —N(C 1-4 alkyl) 2 , OR 11 , NHOR 11 , C(O)R 11 , C(O)NR 11 R 11 , C(O)OR 11 , OC(O)R 11 , OC(O)NR 11 R 11 , NR 11 C(O)R 11 , NR 11 C(O)OR 11 , NR 11 C(O)NR 11 R 11 , C(═NR 11 )R 11 , C(═NR 11 )NR 11 R 11 , NR 11 C(═NR 11 )NR 11 R 11 , NR 11 S(O)R 11 , NR 11 S(O) 2 R 11 , NR 11 S(O) 2 NR 11 R 11 , S(O)R 11 , S(O)NR 11 R 11 , S(O) 2 R 11 , and S(O) 2 NR 11 R 11 , wherein each R 11 is independently selected from H and C 1-4 alkyl optionally substituted with 1 or 2 halo, OH, CN or OCH 3 ;
each R 8 is independently selected from H, C 1-4 alkyl, C 3-6 cycloalkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo, CN, OH, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, NH 2 , —NH—C 1-4 alkyl, —N(C 1-4 alkyl) 2 , OR 10 , NHOR 10 , C(O)R 10 , C(O)NR 10 R 10 , C(O)OR 10 , OC(O)R 10 , OC(O)NR 10 R 10 , NR 10 C(O)R 10 , NR 10 C(O)OR 10 NR 10 C(O)NR 10 R 10 , C(═NR 10 )R 10 , C(═NR 10 )NR 10 R 10 , NR 10 C(═NR 10 )NR 10 R 10 , NR 10 S(O)R 10 , NR 10 S(O) 2 R 10 , NR 10 S(O) 2 NR 10 R 10 , S(O)R 10 , S(O)NR 10 R 10 , S(O) 2 R 10 , and S(O) 2 NR 10 R 10 , wherein each R 10 is independently H or C 1-4 alkyl optionally substituted with 1 or 2 groups independently selected from halo, OH, CN and C 1-4 alkoxy and wherein the C 1-4 alkyl, C 3-6 cycloalkyl, C 2-4 alkenyl and C 2-4 alkynyl of R 8 are each optionally substituted with 1 or 2 substituents independently selected from halo, OH, CN, C 1-4 alkyl and C 1-4 alkoxy;
or two adjacent R 9 substituents together with the carbon atoms to which they are attached, form a fused phenyl ring, a fused 5- to 7-membered heterocycloalkyl ring, a fused 5- or 6-membered heteroaryl ring or a fused C 3-10 cycloalkyl ring, wherein the fused 5- to 7-membered heterocycloalkyl ring and fused 5- or 6-membered heteroaryl ring each have 1-4 heteroatoms as ring members selected from N, O and S and wherein the fused phenyl ring, fused 5- to 7-membered heterocycloalkyl ring, fused 5- or 6-membered heteroaryl ring and fused C 3-10 cycloalkyl ring are each optionally substituted with 1 or 2 independently selected R q substituents;
each R a is independently selected from H, CN, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R a are each optionally substituted with 1, 2, 3, 4, or 5 R d substituents;
each R d is independently selected from C 1-4 alkyl, C 1-4 haloalkyl, halo, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, phenyl, 5- or 6-membered heteroaryl, CN, NH 2 , NHOR e , OR e , SR e , C(O)R e , C(O)NR e R e , C(O)OR e , OC(O)R e , OC(O)NR e R e , NHR e , NR e R e , NR e C(O)R e , NR e C(O)NR e R e , NR e C(O)OR e , C(═NR e )NR e R e , NR e C(═NR e )NR e R e , S(O)R e , S(O)NR e R e , S(O) 2 R e , NR e S(O) 2 R e , NR e S(O) 2 NR e R e , and S(O) 2 NR e R e , wherein the C 1-4 alkyl, C 3-10 cycloalkyl, phenyl, 5- or 6-membered heteroaryl and 4-10 membered heterocycloalkyl of R d are each further optionally substituted with 1-3 independently selected R q substituents;
each R b substituent is independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, OH, NH 2 , NO 2 , NHOR c , OR c , SR c , C(O)R c , C(O)NR c R c , C(O)OR c , OC(O)R c , OC(O)NR c R c , C(═NR c )NR c R c , NR c C(═NR c )NR c R c , NHR c , NR c R c , NR c C(O)R c , NR c C(O)OR c , NR c C(O)NR c R c , NR c S(O)R c , NR c S(O) 2 R c , NR c S(O) 2 NR c R c , S(O)R c , S(O)NR c R c , S(O) 2 R c or S(O) 2 NR c R c ; wherein the C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R b are each further optionally substituted with 1-3 independently selected R d substituents;
each R c is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R c are each optionally substituted with 1, 2, 3, 4, or 5 R f substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, halo, CN, NHOR g , OR g , SR g , C(O)R g , C(O)NR g R g , C(O)OR g , OC(O)R g , OC(O)NR g R g , NHR g , NR g R g , NR g C(O)R g , NR g C(O)NR g R g , NR g C(O)OR g , C(═NR g )NR g R g , NR g C(═NR g )NR g R g , S(O)R g , S(O)NR g R g , S(O) 2 R, NR g S(O) 2 R g , NR g S(O) 2 NR g R g , and S(O) 2 NR g R g ; wherein the C 1-4 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R f are each optionally substituted with 1, 2, 3, 4, or 5 R n substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, halo, CN, R o , NHOR o , OR o , SR o , C(O)R o , C(O)NR o R o , C(O)OR o , OC(O)R o , OC(O)NR o R o , NHR o , NR o R o , NR o C(O)R o , NR o C(O)NR o R o , NR o C(O)OR o , C(═NR)NR o R o , NR o C(═NR o )NR o R o , S(O)R o , S(O)NR o R o , S(O) 2 R o , NR o S(O) 2 R o , NR o S(O) 2 NR o R o , and S(O) 2 NR o R o ;
each R g is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl- and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R g are each optionally substituted with 1-3 independently selected R p substituents;
or any two R a substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 R h substituents independently selected from C 1-6 alkyl, C 3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-6 membered heteroaryl)-C 1-4 alkyl-, (4-7 membered heterocycloalkyl)-C 1-4 alkyl-, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo, CN, OR i , SR i , NHOR i , C(O)R i , C(O)NR i R i , C(O)OR i , OC(O)R i , OC(O)NR i R i , NHR i , NR i R i , NR i C(O)R i , NR i C(O)NR i R i , NR i C(O)OR i , C(═NR i )NR i R i , NR i C(═NR i )NR i R i , S(O)R i , S(O)NR i R i , S(O) 2 R i , NR i S(O) 2 R i , NR i S(O) 2 NR i R i , and S(O) 2 NR i R i , wherein the C 1-6 alkyl, C 3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-6 membered heteroaryl)-C 1-4 alkyl-, and (4-7 membered heterocycloalkyl)-C 1-4 alkyl- of R h are each further optionally substituted by 1, 2, or 3 R j substituents independently selected from C 3-6 cycloalkyl, C 6-10 aryl, 5 or 6-membered heteroaryl, C 2-4 alkenyl, C 2-4 alkynyl, halo, C 1-4 alkyl, C 1-4 haloalkyl, CN, NHOR k , OR k , SR k , C(O)R k , C(O)NR k R k , C(O)OR k , OC(O)R k , OC(O)NR k R k , NHR k , NR k R k , NR k C(O)R k , NR k C(O)NR k R k , NR k C(O)OR k , C(═NR k )NR k R k , NR k C(═NR k )NR k R k , S(O)R k , S(O)NR k R k , S(O) 2 R k , NR k S(O) 2 R k , NR k S(O) 2 NR k R k , and S(O) 2 NR k R k ; or two R h groups attached to the same carbon atom of the 4- to 10-membered heterocycloalkyl taken together with the carbon atom to which they are attached form a C 3-6 cycloalkyl or 4- to 6-membered heterocycloalkyl having 1-2 heteroatoms as ring members selected from O, N or S;
or any two R c substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;
or any two R e substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;
or any two R g substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;
or any two R i substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;
or any two R k substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;
or any two R o substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents; and
each R e , R i , R k , R o or R p is independently selected from H, C 1-4 alkyl, C 3-6 cycloalkyl, C 6-10 aryl, 5 or 6-membered heteroaryl, C 1-4 haloalkyl, C 2-4 alkenyl, and C 2-4 alkynyl, wherein the C 1-4 alkyl, C 3-6 cycloalkyl, C 6-10 aryl, 5 or 6-membered heteroaryl, C 2-4 alkenyl, and C 2-4 alkynyl of R e , R i , R k , R o or R p are each optionally substituted with 1, 2 or 3 R q substituents;
each R q is independently selected from OH, CN, —COOH, NH 2 , halo, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylthio, phenyl, 4- to 6-membered heterocycloalkyl, 5- or 6-membered heteroaryl, C 3-6 cycloalkyl, NHR 12 , NR 12 R 12 , and C 1-4 haloalkoxy, wherein the C 1-4 alkyl, phenyl, 4- to 6-membered heterocycloalkyl and 5- or 6-membered heteroaryl of R q are each optionally substituted with 1 or 2 substituents independently selected from halo, OH, CN, —COOH, NH 2 , C 1-4 alkyl, C 1-4 alkoxy, C 3-10 cycloalkyl and 4-, 5-, or 6-membered heterocycloalkyl and each R 12 is independently C 1-6 alkyl;
the subscript n is an integer of 1, 2, 3, 4 or 5; and
the subscript m is an integer of 1, 2 or 3.
4 . The compound of any one of claims 1 - 3 , having Formula (II):
wherein R 2 is halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO 2 , OR a , SR a , NHOR a , C(O)R a , C(O)NR a R a , C(O)OR a , OC(O)R a , OC(O)NR a R a , NHR a , NR a R a , NR a C(O)R a , NR a C(O)OR a , NR a C(O)NR a R a , C(═NR a )R a , C(═NR a )NR a R a , NR a C(═NR a )NR a R a , NR a S(O)R a , NR a S(O) 2 R a , NR a S(O) 2 NR a R a , S(O)R a , S(O)NR a R a , S(O) 2 R a , and S(O) 2 NR a R a , wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R 2 are each optionally substituted with 1, 2, 3, or 4 R b substituents, or a pharmaceutically acceptable salt or a stereoisomer thereof.
5 . The compound of any one of claims 1 - 4 , having Formula (III):
or a pharmaceutically acceptable salt or a stereoisomer thereof.
6 . The compound of any one of claims 1 - 5 , having Formula (IV):
or a pharmaceutically acceptable salt or a stereoisomer thereof.
7 . The compound of any one of claim 1 - 4 , having Formula (V):
or a pharmaceutically acceptable salt or a stereoisomer thereof.
8 . The compound of any one of claims 1 - 4 and 7 , having Formula (VI):
or a pharmaceutically acceptable salt or a stereoisomer thereof.
9 . The compound of any one of claims 1 - 8 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the moiety
is selected from
10 . The compound of any one of claims 1 - 3 , having Formula (VII):
wherein R 3 is halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO 2 , OR a , SR a , NHOR a , C(O)R a , C(O)NR a R a , C(O)OR a , OC(O)R a , OC(O)NR a R a , NHR a , NR a R a , NR a C(O)R a , NR a C(O)OR a , NR a C(O)NR a R a , C(═NR a )R a , C(═NR a )NR a R a , NR a C(═NR a )NR a R a , NR a S(O)R a , NR a S(O) 2 R a , NR a S(O) 2 NR a R a , S(O)R a , S(O)NR a R a , S(O) 2 R a , and S(O) 2 NR a R a , wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-14 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- of R 3 are each optionally substituted with 1, 2, 3, or 4 R b substituents, or a pharmaceutically acceptable salt or a stereoisomer thereof.
11 . The compound of any one of claims 1 - 3 and 10 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the moiety
selected from:
12 . The compound of any one of claims 1 - 8 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein X 1 is CR 1 , X 3 is CR 3 , X 4 is CR 4 , X 5 is CR 5 and X 6 is CR 6 .
13 . The compound of any one of claims 1 - 8 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein X 1 is CR 1 , X 3 is CR 3 , X 4 is CR 4 , X 5 is CR 5 and X 6 is N.
14 . The compound of any one of claims 1 - 8 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein X 1 is CR 1 , X 3 is CR 3 , X 4 is N, X 5 is CR 5 and X 6 is N.
15 . The compound of any one of claims 1 - 8 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein X 1 is CR 1 , X 3 is N, X 4 is CR 4 , X 5 is CR 5 and X 6 is N.
16 . The compound of any one of claims 1 - 8 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein X 1 is CR 1 , X 3 is N, X 4 is CR 4 , X 5 is CR 5 and X 6 is CR 6 .
17 . The compound of any one of claims 1 - 9 and 12 - 16 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 1 , R 3 , R 4 , R 5 and R 6 when applicable, are each independently selected from H, CN, C 1-6 alkyl and halo.
18 . The compound of claim 10 or 11 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 1 , R 2 , R 4 , R 5 and R 6 , when applicable, are each independently selected from H, CN, C 1-6 alkyl and halo.
19 . The compound of any one of claims 1 - 18 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 2 is —CH 2 —R b .
20 . The compound of claim 19 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R b is —NR c R c .
21 . The compound of any one of claims 1 - 14 and 17 - 20 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 3 is —CH 2 —R b .
22 . The compound of claim 21 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R b is —NR c R c .
23 . The compound of any one of claims 1 - 22 or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 2 is 2-hydroxyethylaminomethyl, 2-carboxypiperidin-1-ylmethyl, (S)-2-carboxypiperidin-1-ylmethyl, (R)-2-carboxypiperidin-1-ylmethyl or (3-cyanobenzyl)oxy.
24 . The compound of any one of claims 1 - 14 , 17 - 21 , and 23 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 3 is 2-hydroxyethylaminomethyl, 2-carboxypiperidin-1-ylmethyl, (S)-2-carboxypiperidin-1-ylmethyl, (R)-2-carboxypiperidin-1-ylmethyl or (3-cyanobenzyl)oxy.
25 . The compound of claim 1 , wherein the compound is selected from:
2-[({8-[(2-methylbiphenyl-3-yl)amino]quinolin-3-yl}methyl)amino]ethanol; 2-[({8-[(2-methylbiphenyl-3-yl)amino]-1,7-naphthyridin-3-yl}methyl)amino]ethanol; 1-({8-[(2-methylbiphenyl-3-yl)amino]-1,7-naphthyridin-3-yl}methyl)piperidine-2-carboxylic acid; 1-({4-[(2-methylbiphenyl-3-yl)amino]pyrido[3,2-d]pyrimidin-7-yl}methyl)piperidine-2-carboxylic acid; 1-({8-[(2-methylbiphenyl-3-yl)amino]-1,7-naphthyridin-4-yl}methyl)piperidine-2-carboxylic acid; 2-[({8-[(2-methylbiphenyl-3-yl)amino]-1,7-naphthyridin-4-yl}methyl)amino]ethanol; 2-[({8-[(2-methylbiphenyl-3-yl)amino]quinolin-4-yl}methyl)amino]ethanol; and 1-({8-[(2-methylbiphenyl-3-yl)amino]quinolin-4-yl}methyl)piperidine-2-carboxylic acid;
or a pharmaceutically acceptable salt or a stereoisomer thereof.
26 . The compound of claim 1 , wherein the compound is selected from:
2-[({4-chloro-8-[(2-methylbiphenyl-3-yl)amino]-1,7-naphthyridin-3-yl}methyl)amino]ethanol; 2-[({4-methoxy-8-[(2-methylbiphenyl-3-yl)amino]-1,7-naphthyridin-3-yl}methyl)amino]ethanol; 1-({4-chloro-8-[(2-methylbiphenyl-3-yl)amino]-1,7-naphthyridin-3-yl}methyl)piperidine-2-carboxylic acid; 2-{[(8-{[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]amino}-1,7-naphthyridin-4-yl)methyl]amino}ethanol; 1-[(8-{[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]amino}-1,7-naphthyridin-4-yl)methyl]piperidine-2-carboxylic acid; 2-[({5-[(2-methylbiphenyl-3-yl)amino]pyrido[3,4-b]pyrazin-2-yl}methyl)amino]ethanol; (2S)-1-({5-[(2-methylbiphenyl-3-yl)amino]pyrido[3,4-b]pyrazin-2-yl}methyl)piperidine-2-carboxylic acid; 2-(2,3-dihydro-1,4-benzodioxin-6-yl)-6-[(3-{[(2-hydroxyethyl)amino]methyl}-1,7-naphthyridin-8-yl)amino]benzonitrile; 2-{[(8-{[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]amino}-1,7-naphthyridin-3-yl)methyl]amino}ethanol; 2-[({8-[(3-cyclohex-1-en-1-yl-2-methylphenyl)amino]-1,7-naphthyridin-3-yl}methyl)amino]ethanol; 3-[(3-{[(2-hydroxyethyl)amino]methyl}-1,7-naphthyridin-8-yl)amino]biphenyl-2-carbonitrile; 2-cyclohex-1-en-1-yl-6-[(3-{[(2-hydroxyethyl)amino]methyl}-1,7-naphthyridin-8-yl)amino]benzonitrile; and 2-cyclohexyl-6-[(3-{[(2-hydroxyethyl)amino]methyl}-1,7-naphthyridin-8-yl)amino]benzonitrile;
or a pharmaceutically acceptable salt or a stereoisomer thereof.
27 . A pharmaceutical composition comprising a compound of any one of claims 1 - 26 , or a pharmaceutically acceptable salt or a stereoisomer thereof, and a pharmaceutically acceptable carrier or excipient.
28 . A method of inhibiting PD-1/PD-L1 interaction, said method comprising administering to a patient a compound of any one of claims 1 - 26 , or a pharmaceutically acceptable salt or a stereoisomer thereof.
29 . A method of treating a disease or disorder associated with PD-1/PD-L1 interaction, said method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of any one of claims 1 - 26 , or a pharmaceutically acceptable salt or a stereoisomer thereof, or a composition of claim 27 .
30 . The method of claim 29 , wherein the disease or disorder is a viral infection or cancer.
31 . A method of enhancing, stimulating, modulating and/or increasing the immune response in a patient, said method comprising administering to the patient in need thereof a therapeutically effective amount of a compound of any one of claims 1 - 26 , or a pharmaceutically acceptable salt or a stereoisomer thereof, or a composition of claim 27 .
32 . A method of inhibiting growth, proliferation, or metastasis of cancer cells in a patient, said method comprising administering to the patient in need thereof a therapeutically effective amount of a compound of any one of claims 1 - 26 , or a pharmaceutically acceptable salt or a stereoisomer thereof, or a composition of claim 27 .Join the waitlist — get patent alerts
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