Heterocyclic compounds as immunomodulators

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.

What 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 ; 
 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 5 independently selected R 6  substituents; 
 R 1 , R 2  and R 3  are each independently selected from H, C 1-4  alkyl, C 3-6  cycloalkyl, C 3-6  cycloalkyl-C 1-4  alkyl-, 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 , 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 selected from H and 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, C 2-4  alkynyl and C 1-4  alkoxy of R 1 , R 2  and R 3  are each optionally substituted with 1 or 2 substituents independently selected from halo, OH, CN and C 1-4  alkoxy; 
 R 4 , R 5  and R 6  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 C(═NOH)NR a R a , NR a C(═NCN)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 4 , R 5  and R 6  are each optionally substituted with 1, 2, 3, 4 or 5 independently selected R b  substituents; 
 or two adjacent R 6  substituents on the Cy ring, taken together with the atoms to which they are attached, form a fused phenyl ring, a fused 5-, 6- or 7-membered heterocycloalkyl ring, a fused 5- or 6-membered heteroaryl ring or a fused C 3-6  cycloalkyl ring, wherein the fused 5-, 6- or 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-, 6- or 7-membered heterocycloalkyl ring, fused 5- or 6-membered heteroaryl ring and fused C 3-6  cycloalkyl ring are each optionally substituted with 1, 2 or 3 independently selected R b  substituents; 
 R 7  and R 8  are each independently 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 11 , SR 11 , NH 2 , —NHR 1 , —N(R 11 ) 2 , 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 C(═NOH)NR 11 R 11 , NR 11 C(═NCN)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 , or 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 7  and R 8  are each optionally substituted with 1, 2 or 3 independently selected R b  substituents; 
 R 9  is 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 12 , SR 12 , C(O)R 12 , C(O)NR 12 R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)NR 12 R 12 , C(═NR 12 )R 12 , C(═NR 12 )NR 12 R 12 , S(O)R 12 , S(O)NR 12 R 12 , S(O) 2 R 12 , or S(O) 2 NR 12 R 12 , 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  are each optionally substituted with 1, 2 or 3 independently selected R b  substituents; 
 R 11  and R 12  are each 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  and R 12  are each optionally substituted with 1, 2 or 3 independently selected R b  substituents; 
 each R a  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 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 a  are each optionally substituted with 1, 2 or 3 independently selected R d  substituents; 
 each R b  substituent is independently selected from halo, C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  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 , NR c C(═NOH)NR c R c , NR c C(═NCN)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  and S(O) 2 NR c R c ; wherein the C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  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 1-6  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 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 c  are each optionally substituted with 1, 2 or 3 R f  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 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 , NR g C(═NOH)NR g R g , NR g C(═NCN)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 1-6  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 f  are each optionally substituted with 1, 2 or 3 R n  substituents independently selected from C 1-6  alkyl, C 1-6  haloalkyl, halo, CN, phenyl, C 3-6  cycloalkyl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, 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 , wherein the C 1-6  alkyl, C 1-6  haloalkyl, phenyl, C 3-6  cycloalkyl, 5-6 membered heteroaryl, and 4-6 membered heterocycloalkyl of R n  is optionally substituted with 1, 2 or 3 R q  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 f  substituents; 
 each R e  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 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 e  are each optionally substituted with 1, 2 or 3 independently selected R f  substituents; 
 each R g  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 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 1-6  haloalkyl, 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 , NR i C(═NOH)NR i R i , NR i C(═NCN)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 1 , NR i S(O) 2 NR i R i , and S(O) 2 NR i R i , wherein the C 1-6  alkyl, C 1-6  haloalkyl, 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- of R h  are each optionally substituted by 1, 2, or 3 R j  substituents independently selected from C 1-4  alkyl, 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  haloalkyl, C 1-4  haloalkoxy, 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 
 or any two R r  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; 
 each R i , R k , R o  or R r  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 3-6  cycloalkyl, C 6-10  aryl, 4-6 membered heterocycloalkyl, 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 1-6  haloalkyl, C 3-6  cycloalkyl, C 6-10  aryl, 4-6 membered heterocycloalkyl, 5 or 6-membered heteroaryl, C 2-4  alkenyl, and C 2-4  alkynyl of R i , R k , R o  or R r  are each optionally substituted with 1, 2 or 3 R q  substituents; and 
 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  haloalkoxy, C 1-6  alkylthio, phenyl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C 3-6  cycloalkyl, NHR 13  and NR 13 R 13 , 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 and 4-6 membered heterocycloalkyl and each R 13  is independently C 1-6  alkyl. 
 
     
     
         2 . The compound of  claim 1 , having Formula (II): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or a stereoisomer thereof. 
     
     
         3 . The compound of  claim 1 , having Formula (III): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or a stereoisomer thereof. 
     
     
         4 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein (i) X 1  is N, X 2  is CR 2  and X 3  is CR 3 ; (ii) X 1  is CR 1 , X 2  is N and X 3  is CR 3 ; or (iii) X 1  is CR 1 , X 2  is CR 2  and X 3  is N. 
     
     
         5 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein (i) X 4  is N and X 5  is N; (ii) X 4  is N and X 5  is CR 5 ; or (iii) X 4  is CR 4  and X 5  is N. 
     
     
         6 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein Cy is phenyl, 5- or 6-membered heteroaryl, C 3-6  cycloalkyl or 5- or 6-membered heterocycloalkyl, each of which is optionally substituted with 1 to 5 independently selected R 6  substituents; or two adjacent R 6  substituents on the Cy ring, taken together with the atoms to which they are attached, form a fused phenyl ring, a fused 5-, 6- or 7-membered heterocycloalkyl ring, a fused 5- or 6-membered heteroaryl ring or a fused C 3-6  cycloalkyl ring, wherein the fused 5-, 6- or 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-, 6- or 7-membered heterocycloalkyl ring, fused 5- or 6-membered heteroaryl ring and fused C 3-6  cycloalkyl ring are each optionally substituted with 1, 2 or 3 independently selected R b  substituents. 
     
     
         7 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein Cy is phenyl, 2-thiophenyl, 3-thiophenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 3,6-dihydro-2H-pyran-4-yl, cyclohexyl, cyclohexenyl, 2,3-dihydro-1,4-benzodioxin-6-yl, 1,3-benzodioxin-5-yl, 2-methylindazol-6-yl or 1-methylindazol-4-yl, each of which is optionally substituted with 1 to 5 independently selected R 6  substituents. 
     
     
         8 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 1 , R 2  and R 3  are each independently selected from H, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, halo, CN, OH, C 1-4  alkoxy, C 1-4  haloalkyl, and C 1-4  haloalkoxy. 
     
     
         9 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 1  is H, R 2  is H or halo, and R 3  is H. 
     
     
         10 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 4  is H, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl or C 1-6  halo alkoxy. 
     
     
         11 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 4  is H. 
     
     
         12 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 5  is H, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl or C 1-6  halo alkoxy. 
     
     
         13 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 5  is H. 
     
     
         14 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 6  is H, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  haloalkoxy, phenyl, C 3-10  cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, phenyl-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 C(═NOH)NR a R a , NR a C(═NCN)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 , or S(O) 2 NR a R a , wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, phenyl, C 3-10  cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, phenyl-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 6  are each optionally substituted with 1, 2, 3, 4 or 5 independently selected R b  substituents; or two adjacent R 6  substituents on the Cy ring, taken together with the atoms to which they are attached, form a fused phenyl ring, a fused 5-, 6- or 7-membered heterocycloalkyl ring, a fused 5- or 6-membered heteroaryl ring or a fused C 3-6  cycloalkyl ring, wherein the fused 5-, 6- or 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-, 6- or 7-membered heterocycloalkyl ring, fused 5- or 6-membered heteroaryl ring and fused C 3-6  cycloalkyl ring are each optionally substituted with 1, 2 or 3 independently selected R b  substituents. 
     
     
         15 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 6  is H, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, CN, NO 2 , or OR a , wherein the C 1-6  alkyl, C 2-6  alkenyl, and C 2-6  alkynyl of R 6  are each optionally substituted with 1, 2, 3, 4 or 5 independently selected R b  substituents; or two adjacent R 6  substituents on the Cy ring, taken together with the atoms to which they are attached, form a fused phenyl ring, a fused 5-, 6- or 7-membered heterocycloalkyl ring, a fused 5- or 6-membered heteroaryl ring or a fused C 3-6  cycloalkyl ring, wherein the fused 5-, 6- or 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-, 6- or 7-membered heterocycloalkyl ring, fused 5- or 6-membered heteroaryl ring and fused C 3-6  cycloalkyl ring are each optionally substituted with 1, 2 or 3 independently selected R b  substituents. 
     
     
         16 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 6  is H, halo, C 1-6  alkyl, or OR a ; or two adjacent R 6  substituents on the Cy ring, taken together with the atoms to which they are attached, form a fused phenyl ring, a fused 5-, 6- or 7-membered heterocycloalkyl ring, wherein the fused 5-, 6- or 7-membered heterocycloalkyl ring has 1-4 heteroatoms as ring members selected from N, O and S and wherein the fused 5-, 6- or 7-membered heterocycloalkyl ring is optionally substituted with 1, 2 or 3 independently selected R b  substituents. 
     
     
         17 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 7  is halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  haloalkoxy, CN, NH 2 , NH(C 1-6  alkyl), N(C 1-6  alkyl) 2 , C 3-6  cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl or phenyl, wherein C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-6  cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl and phenyl are each optionally substituted with 1, 2 or 3 independently selected R q  substituents. 
     
     
         18 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 7  is halo, C 1-6  alkyl, or CN. 
     
     
         19 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 7  is C 1-6  alkyl or CN. 
     
     
         20 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 8  is C 1-6  alkyl or (4-10 membered heterocycloalkyl)-C 1-4  alkyl-, wherein the C 1-6  alkyl and (4-10 membered heterocycloalkyl)-C 1-4  alkyl- are each optionally substituted with 1, 2 or 3 independently selected R b  substituents. 
     
     
         21 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 8  is C 1-6  alkyl substituted with R b . 
     
     
         22 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 8  is —CH 2 NHR c  or —CH 2 NR c R c . 
     
     
         23 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 8  is (2-hydroxyethylamino)methyl, 2-carboxy-1-piperidinyl, (S)-2-carboxy-1-piperidinyl or (R)-2-carboxy-1-piperidinyl. 
     
     
         24 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 9  is C 1-6  alkyl. 
     
     
         25 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein:
 X 1  is CR 1 ;   X 2  is CR 2 ;   X 3  is CR 3 ;   X 4  is N or CR 4 ;   X 5  is N or CR 5 ;   Cy is phenyl, C 3-6  cycloalkyl, 5- to 6-membered heteroaryl, or 4- to 6-membered heterocycloalkyl, each of which is optionally substituted with 1 to 5 independently selected R 6  substituents;   or two adjacent R 6  substituents on the Cy ring, taken together with the atoms to which they are attached, form a fused 5-, 6- or 7-membered heterocycloalkyl ring, or a fused 5- or 6-membered heteroaryl ring, wherein the fused 5-, 6- or 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 5-, 6- or 7-membered heterocycloalkyl ring and fused 5- or 6-membered heteroaryl ring are each optionally substituted with 1 or 2 independently selected R b  substituents;   R 1 , R 2  and R 3  are each independently selected from H, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, halo, CN, OH, COOH, C 1-4  alkoxy, C 1-4  haloalkyl, C 1-4  haloalkoxy, cyclopropyl, cyclopropylmethyl, NH 2 , —NHC 1-4  alkyl, —N(C 1-4  alkyl) 2 , —C(O)R 10 , —O(CO)R 10 , —C(O)OR 10 , —O(CO)NHR 10 , —NHC(O)OR 10 , —NHC(O)NHR 10 , —C(O)NHR 10 , —NHC(O)R 10 , —SO 2 R 10 , NHSO 2 R 10  and —SO 2 NHR 10 , wherein the C 1-4  alkyl, cyclopropyl and cyclopropylmethyl of R 1 , R 2  or R 3  are each optionally substituted with halo, OH, CN or C 1-4  alkoxy;   R 4 , R 5  and R 6  are each independently selected from H, halo, C 1-6  alkyl, C 1-6  alkoxy, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  haloalkoxy, phenyl, C 3-6  cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C 1-4  alkyl-, C 3-6  cycloalkyl-C 1-4  alkyl-, (5-6 membered heteroaryl)-C 1-4  alkyl-, (4-6 membered heterocycloalkyl)-C 1-4  alkyl-, CN, OH, COOH, NO 2 , OR a , C(O)OR a , NH 2 , —NHR a , —N(R a ) 2 , —C(O)R a , —O(CO)R a , —C(O)OR a , —O(CO)NR a R a , —NHC(O)OR a , —NHC(O)NR a R a , —C(O)NR a R a , —NHC(O)R a , —SO 2 R a , —NHSO 2 R a  and —SO 2 NR a R a , wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, phenyl, C 3-6  cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C 1-4  alkyl-, C 3-6  cycloalkyl-C 1-4  alkyl-, (5-6 membered heteroaryl)-C 1-4  alkyl- and (4-6 membered heterocycloalkyl)-C 1-4  alkyl- of R 4 , R 5  and R 6  are each optionally substituted with 1 or 2 R b  substituents;   R 7  is halo, C 1-6  alkyl, CN, C 3-6  cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, C 3-6  cycloalkyl-C 1-4  alkyl-, (4-6 membered heterocycloalkyl)-C 1-4  alkyl-, or (5-6 membered heteroaryl)-C 1-4  alkyl, wherein C 1-6  alkyl, C 3-6  cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, C 3-6  cycloalkyl-C 1-4  alkyl-, (4-6 membered heterocycloalkyl)-C 1-4  alkyl- and (5-6 membered heteroaryl)-C 1-4  alkyl of R 7  are each optionally substituted with 1 or 2 substituents independently selected from halo, C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  haloalkoxy, CN, OH, NH 2 , —NH(C 1-6  alkyl), —N(C 1-6  alkyl) 2 , COOH, —OC 1-6  alkyl, —SC 1-6  alkyl, C(O)NH 2 , —C(O)NH(C 1-6  alkyl), —C(O)NH(C 1-6  alkyl) 2 , —C(O)OC 1-6  alkyl, —OC(O)NHC 1-6  alkyl, —OC(O)NH 2 , —OC(O)NH(C 1-6  alkyl) 2 , —NHC(O)C 1-6  alkyl, —NHC(O)H, —N(C 1-6  alkyl)C(O)C 1-6  alkyl, —NHC(O)OC 1-6  alkyl, —N(C 1-6  alkyl)C(O)OC 1-6  alkyl, —NHC(O)NH(C 1-6  alkyl), —NHC(O)N(C 1-6  alkyl) 2 , —NHC(O)NH 2 , —N(C 1-6  alkyl)C(O)NH(C 1-6  alkyl), —N(C 1-6  alkyl)C(O)N(C 1-6  alkyl) 2 , —N(C 1-6  alkyl)C(O)NH 2 , —NHS(O) 2 (C 1-6  alkyl), —N(C 1-6  alkyl)S(O) 2 (C 1-6  alkyl), —NHS(O) 2 NH 2 , —NHS(O) 2 NH(C 1-6  alkyl), —NHS(O) 2 N(C 1-6  alkyl) 2 , —N(C 1-6  alkyl)S(O) 2 NH 2 , —N(C 1-6  alkyl)S(O) 2 NH(C 1-6  alkyl), —N(C 1-6  alkyl)S(O) 2 N(C 1-6  alkyl) 2 , —S(O) 2 (C 1-6  alkyl), —S(O) 2 NH 2 , —S(O) 2 NH(C 1-6  alkyl) and —S(O) 2 N(C 1-6  alkyl) 2 ;   R 8  is halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  haloalkoxy, phenyl, 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 , NH 2 , —NHR 11 , —N(R 11 ) 2 , C(O)NR 11 R 11 , C(O)OR 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 , NR 11 S(O)R 11 , NR 11 S(O) 2 R 11 , NR 11 S(O) 2 NR 11 R 11 , S(O) 2 R 11 , or 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, phenyl, 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 8  are each optionally substituted with 1, 2 or 3 R b  substituents;   R 9  is C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, phenyl, C 3-6  cycloalkyl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, phenyl-C 1-4  alkyl-, C 3-6  cycloalkyl-C 1-4  alkyl-, (5-6 membered heteroaryl)-C 1-4  alkyl- or (4-6 membered heterocycloalkyl)-C 1-4  alkyl-, each of which is 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, phenyl, C 3-6  cycloalkyl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, phenyl-C 1-4  alkyl-, C 3-6  cycloalkyl-C 1-4  alkyl-, (5-6 membered heteroaryl)-C 1-4  alkyl-, and (4-6 membered heterocycloalkyl)-C 1-4  alkyl-, wherein the C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, phenyl, C 3-6  cycloalkyl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, phenyl-C 1-4  alkyl-, C 3-6  cycloalkyl-C 1-4  alkyl-, (5-6 membered heteroaryl)-C 1-4  alkyl- and (4-6 membered heterocycloalkyl)-C 1-4  alkyl- of R 11  are each optionally substituted with 1 or 2 R b  substituents;   each R a  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, phenyl, C 3-6  cycloalkyl, 4-6 membered heterocycloalkyl and 5-6 membered hetero aryl;   each R b  is independently selected from halo, C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  haloalkoxy, CN, OH, NH 2 , NHR c , N(R c ) 2 , OR c , C(O)NR c R c , C(O)OR c , COOH, NR c C(O)R c , OC(O)NR c R c , NR c C(O)OR c , NR c C(O)NR c R c , NR c S(O) 2 R c , NR c S(O) 2 NR c R c , S(O) 2 R c  and S(O) 2 NR c R c ;   each R c  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, phenyl, C 3-6  cycloalkyl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, phenyl-C 1-4  alkyl-, C 3-6  cycloalkyl-C 1-4  alkyl-, (5-6 membered heteroaryl)-C 1-4  alkyl-, and (4-6 membered heterocycloalkyl)-C 1-4  alkyl-, wherein the C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, phenyl, C 3-6  cycloalkyl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, phenyl-C 1-4  alkyl-, C 3-6  cycloalkyl-C 1-4  alkyl-, (5-6 membered heteroaryl)-C 1-4  alkyl- and (4-6 membered heterocycloalkyl)-C 1-4  alkyl- of R c  are each optionally substituted with 1 or 2 R f  substituents;   or 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 or 2 independently selected R h  substituents;   each R f  is independently selected from halo, C 1-6  alkyl, C 1-6  alkoxy, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  haloalkoxy, phenyl, C 3-6  cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, CN, OH, COOH, OR g , C(O)OR g , NH 2 , —NHR g , —N(R g ) 2 , —C(O)NR g R g , —NR g C(O)R g , OC(O)NR g R g , NR g C(O)OR g , NR g C(O)NR g R g , NR g S(O) 2 R g , NR g S(O) 2 NR g R g , S(O) 2 R and S(O) 2 NR g R g , wherein each R g  is independently H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, or C 2-6  alkynyl; and   each R h  is independently selected from halo, C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  haloalkoxy, CN, OH, NH 2 , NHR i , N(R i ) 2 , OR i , C(O)NR i R i , NR i C(O)R i  and C(O)OR i , wherein R i  is H or C 1-6  alkyl.   
     
     
         26 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein:
 X 1  is CR 1 ;   X 2  is CR 2 ;   X 3  is CR 3 ;   X 4  is CR 4 ;   X 5  is CR 5 ;   Cy is phenyl, C 3-10  cycloalkyl, 5- to 14-membered heteroaryl, or 4- to 10-membered heterocycloalkyl, each of which is optionally substituted with 1 to 5 independently selected R 6  substituents;   R 1 , R 2  and R 3  are each independently selected from H, C 1-4  alkyl, 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, and —N(C 1-4  alkyl) 2 , wherein the C 1-4  alkyl, C 3-6  cycloalkyl, C 2-4  alkenyl, C 2-4  alkynyl and C 1-4  alkoxy of R 1 , R 2  and R 3  are each optionally substituted with 1 or 2 substituents independently selected from halo, OH, CN and C 1-4  alkoxy;   R 4 , R 5  and R 6  are each independently selected from H, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, CN, NO 2 , and OR a , wherein the C 1-6  alkyl, C 2-6  alkenyl, and C 2-6  alkynyl of R 4 , R 5  and R 6  are each optionally substituted with 1, 2, 3, 4 or 5 independently selected R b  substituents;   or two adjacent R 6  substituents on the Cy ring, taken together with the atoms to which they are attached, form a fused phenyl ring, a fused 5-, 6- or 7-membered heterocycloalkyl ring, a fused 5- or 6-membered heteroaryl ring or a fused C 3-6  cycloalkyl ring, wherein the fused 5-, 6- or 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-, 6- or 7-membered heterocycloalkyl ring, fused 5- or 6-membered heteroaryl ring and fused C 3-6  cycloalkyl ring are each optionally substituted with 1, 2 or 3 independently selected R b  substituents;   R 7  and R 8  are each independently 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 NO 2 , 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 7  and R 8  are each optionally substituted with 1, 2 or 3 independently selected R b  substituents;   R 9  is C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, or C 1-6  haloalkoxy, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, and C 1-6  haloalkoxy of R 9  are each optionally substituted with 1, 2 or 3 independently selected R b  substituents;   each R a  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, and C 2-6  alkynyl;   each R b  substituent is independently selected from halo, C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  haloalkoxy, 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 , and OC(O)NR c R c ;   each R c  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, and C 2-6  alkynyl, wherein the C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, and C 2-6  alkynyl of R c  are each optionally substituted with 1, 2 or 3 R f  substituents independently selected from C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, 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 , and NR g C(O)R g ; and   each R g  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, and C 2-6  alkynyl.   
     
     
         27 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein:
 X 1  is CR 1 ;   X 2  is CR 2 ;   X 3  is CR 3 ;   X 4  is CR 4 ;   X 5  is CR 5 ;   Cy is phenyl, C 3-10  cycloalkyl, 5- to 14-membered heteroaryl, or 4- to 10-membered heterocycloalkyl, each of which is optionally substituted with 1 to 5 independently selected R 6  substituents;   R 1 , R 2  and R 3  are each independently selected from H, halo, C 1-4  alkyl, C 2-4  alkenyl, and C 2-4  alkynyl;   R 4 , R 5  and R 6  are each independently selected from H, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, and OR a ;   or two adjacent R 6  substituents on the Cy ring, taken together with the atoms to which they are attached form a fused 5-, 6- or 7-membered heterocycloalkyl ring, wherein the fused 5-, 6- or 7-membered heterocycloalkyl ring has 1-4 heteroatoms as ring members selected from N, O and S and wherein the fused 5-, 6- or 7-membered heterocycloalkyl ring is optionally substituted with 1, 2 or 3 independently selected R b  substituents;   R 7  and R 8  are each independently halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, (4-10 membered heterocycloalkyl)-C 1-4  alkyl-, or CN, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, and (4-10 membered heterocycloalkyl)-C 1-4  alkyl- of R 7  and R 8  are each optionally substituted with 1, 2 or 3 independently selected R b  substituents;   R 9  is C 1-6  alkyl, C 2-6  alkenyl, or C 2-6  alkynyl;   each R a  is independently selected from H and C 1-6  alkyl;   each R b  substituent is independently selected from halo, C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  haloalkoxy, OH, OR c , C(O)R c , C(O)NR c R c , and C(O)OR c ;   each R c  is independently selected from H, C 1-6  alkyl, C 2-6  alkenyl, and C 2-6  alkynyl, wherein the C 1-6  alkyl, C 2-6  alkenyl, and C 2-6  alkynyl of R c  are each optionally substituted with 1, 2 or 3 R f  substituents independently selected from OR g , C(O)R g , C(O)NR g R g , and C(O)OR g ; and   each R g  is independently selected from H, C 1-6  alkyl, C 2-6  alkenyl, and C 2-6  alkynyl.   
     
     
         28 . The compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein:
 X 1  is CR 1 ;   X 2  is CR 2 ;   X 3  is CR 3 ;   X 4  is CR 4 ;   X 5  is CR 5 ;   Cy is phenyl, C 3-10  cycloalkyl, 5- to 14-membered heteroaryl, or 4- to 10-membered heterocycloalkyl, each of which is optionally substituted with 1 to 5 independently selected R 6  substituents;   R 1 , R 2  and R 3  are H;   R 4 , R 5  and R 6  are each independently selected from H, halo, C 1-6  alkyl, and OR a ;   or two adjacent R 6  substituents on the Cy ring, taken together with the atoms to which they are attached form a fused 5-, 6- or 7-membered heterocycloalkyl ring, wherein the fused 5-, 6- or 7-membered heterocycloalkyl ring has 1-4 heteroatoms as ring members selected from N, O and S and wherein the fused 5-, 6- or 7-membered heterocycloalkyl ring is optionally substituted with 1, 2 or 3 independently selected R b  substituents;   R 7  and R 8  are each independently C 1-6  alkyl, (4-10 membered heterocycloalkyl)-C 1-4  alkyl-, or CN, wherein the C 1-6  alkyl and (4-10 membered heterocycloalkyl)-C 1-4  alkyl- of R 7  and R 8  are each optionally substituted with 1, 2 or 3 independently selected R b  substituents;   R 9  is C 1-6  alkyl;   each R a  is C 1-6  alkyl;   each R b  is independently selected from C 1-6  alkyl and C(O)OR c ;   each R c  is independently selected from H and C 1-6  alkyl, wherein the C 1-6  alkyl of R c  is optionally substituted with 1, 2 or 3 R f  substituents independently selected from OR g ; and   each R g  is H.   
     
     
         29 . The compound of  claim 1 , selected from:
 (2S)-1-[(1-methyl-5-{[(2-methylbiphenyl-3-yl)amino]carbonyl}-6-oxo-1,6-dihydropyridin-3-yl)methyl]piperidine-2-carboxylic acid;   5-{[(2-hydroxyethyl)amino]methyl}-1-methyl-N-(2-methylbiphenyl-3-yl)-2-oxo-1,2-dihydropyridine-3-carboxamide;   N-(2-cyano-3-cyclohexylphenyl)-5-{[(2-hydroxyethyl)amino]methyl}-1-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide;   N-[2-cyano-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-5-{[(2-hydroxyethyl)amino]methyl}-1-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide;   N-(2-cyano-3′-methoxybiphenyl-3-yl)-5-{[(2-hydroxyethyl)amino]methyl}-1-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide;   N-(2-cyano-2′-fluorobiphenyl-3-yl)-5-{[(2-hydroxyethyl)amino]methyl}-1-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide;   N-(2-cyanobiphenyl-3-yl)-5-{[(2-hydroxyethyl)amino]methyl}-1-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide;   N-(2-cyano-3-(1-methyl-1H-indazol-4-yl)phenyl)-5-((2-hydroxyethylamino)methyl)-1-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide;   (2S)-1-[(1-ethyl-5-{[(2-methylbiphenyl-3-yl)amino]carbonyl}-6-oxo-1,6-dihydropyridin-3-yl)methyl]piperidine-2-carboxylic acid;   1-ethyl-5-{[(2-hydroxyethyl)amino]methyl}-N-(2-methylbiphenyl-3-yl)-2-oxo-1,2-dihydropyridine-3-carboxamide;   5-{[(2-hydroxyethyl)amino]methyl}-1-methyl-N-[2-methyl-3-(1-methyl-1H-indazol-4-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxamide;   N-(2′-fluoro-3′-methoxy-2-methylbiphenyl-3-yl)-5-((2-hydroxyethylamino)methyl)-1-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide; and   N-[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]-5-{[(2-hydroxyethyl)amino]methyl}-1-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide,   or a pharmaceutically acceptable salt or a stereoisomer thereof.   
     
     
         30 . A pharmaceutical composition comprising a compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, and at least one pharmaceutically acceptable carrier or excipient. 
     
     
         31 . A method of inhibiting PD-1/PD-L1 interaction, said method comprising administering to a patient a compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof. 
     
     
         32 . A method of treating a disease or disorder associated with inhibition of PD-1/PD-L1 interaction, said method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof. 
     
     
         33 . A method of enhancing, stimulating 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  claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof.