Heterocyclic compounds as immunomodulators

A compound of Formula (I):

• or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein:
• X1 is O, S, N, NR1 or CR1;
• X2 is N or C;
• X3 is O, S, N, NR3 or CR3;
• X4 is N or CR4;
• X5 is N or CR5;
• X6 is N or CR6;
• Y is C or N;
• at least one of X1, X2, X3 and Y is a heteroatom selected from N, O and S, wherein N is optionally substituted by R1 or R3;
• Cy is C6-10 aryl, C3-10 cycloalkyl, 5- to 14-membered heteroaryl, or 4- to 10-membered heterocycloalkyl, each of which is optionally substituted with 1 to 5 independently selected R7 substituents;
• R1, R3, R4, R5 and R6 are each independently selected from H, C1-4 alkyl, C3-4 cycloalkyl, C2-4 alkenyl, C2-4 alkynyl, halo, CN, OH, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, NH2, —NH—C1-4 alkyl, —N(C1-4 alkyl)2, NHOR10, C(O)R10, C(O)NR10R10, C(O)OR10, OC(O)R10, OC(O)NR10R10, NR10C(O)R10, NR10C(O)OR10, NR10C(O)NR10R10, C(═NR10)R10, C(═NR10)NR10R10, NR10C(═NR10)NR10R10, NR10S(O)R10, NR10S(O)2R10, NR10S(O)2NR10R10, S(O)R10, S(O)NR10R10, S(O)2R10, and S(O)2NR10R10, wherein each R10 is independently selected from H and C1-4 alkyl optionally substituted with 1 or 2 groups independently selected from halo, OH, CN and C1-4 alkoxy;
• and wherein the C1-4 alkyl, C3-4 cycloalkyl, C2-4 alkenyl, C2-4 alkynyl and C1-4 alkoxy of R1, R3, R4, R5 and R6 are each optionally substituted with 1 or 2 substituents independently selected from halo, OH, CN and C1-4 alkoxy;
• R9 is C1-4 alkyl, halo, CN, OH, cyclopropyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, NH2, —NH—C1-4 alkyl, —N(C1-4 alkyl)2, NHOR11, C(O)R11, C(O)NR11R11, C(O)OR11, OC(O)R11, OC(O)NR11R11, NR11C(O)R11, NR11C(O)OR11, NR11C(O)NR11R11, C(═NR11)R11, C(═NR11)NR11R11, NR11C(═NR11)NR11R11, NR11S(O)R11, NR11S(O)2R11, NR11S(O)2NR11R11, S(O)R11, S(O)NR11R11, S(O)2R11, and S(O)2NR11R11, wherein C1-4 alkyl, cyclopropyl, C2-4 alkenyl, C2-4 alkynyl and C1-4 alkoxy of R9 are each optionally substituted with 1 or 2 substituents selected from halo, OH, CN and OCH3 and each R11 is independently selected from H and C1-4 alkyl optionally substituted with 1 or 2 halo, OH, CN or OCH3 substituents;
• R7, R13 and R14 are each independently selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-14 membered heteroaryl)-C1-4 alkyl-, (4-10 membered heterocycloalkyl)-C1-4 alkyl-, CN, NO2, ORa, SRa, NHORa, C(O)Ra, C(O)NRaRa, C(O)ORa, OC(O)Ra, OC(O)NRaRa, NHRa, NRaRa, NRaC(O)Ra, NRaC(O)ORa, NRaC(O)NRaRa, C(═NRa)Ra, C(═NRa)NRaRa, NRaC(═NRa)NRaRa, NRaS(O)Ra, NRaS(O)2Ra, NRaS(O)2NRaRa, S(O)Ra, S(O)NRaRa, S(O)2Ra, and S(O)2NRaRa, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-14 membered heteroaryl)-C1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl- of R7, R13 and R14 are each optionally substituted with 1, 2, 3, or 4 Rb substituents;
• or two adjacent R7 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 C3-6 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 C3-6 cycloalkyl ring are each optionally substituted with 1, 2 or 3 independently selected Rb substituents;
• or two R13 substituents attached to the same carbon atom, taken together with the carbon atom to which they are attached, form a C3-6 cycloalkyl ring or 4-, 5-, 6- or 7-membered heterocycloalkyl ring, wherein the C3-6 cycloalkyl ring and 4-, 5-, 6- or 7-membered heterocycloalkyl ring are each optionally substituted with 1, 2 or 3 independently selected Rb substituents;
• each Ra is independently selected from H, CN, C1-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl- and (4-10 membered heterocycloalkyl)-C1-4 alkyl- of Ra are each optionally substituted with 1, 2, 3, 4, or 5 Rd substituents;
• each Rd is independently selected from C1-4 alkyl, C1-4 haloalkyl, halo, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, CN, NH2, NHORe, ORe, SRe, C(O)Re, C(O)NReRe, C(O)ORe, OC(O)Re, OC(O)NReRe, NHRe, NReRe, NReC(O)Re, NReC(O)NReRe, NReC(O)ORe, C(═NRe)NReRe, NReC(═NRe)NReRe, S(O)Re, S(O)NReRe, S(O)2Re, NReS(O)2Re, NReS(O)2NReRe, and S(O)2NReRe, wherein the C1-4 alkyl, C3-10 cycloalkyl and 4-10 membered heterocycloalkyl of Rd are each further optionally substituted with 1-3 independently selected Rq substituents;
• each Rb substituent is independently selected from halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, (4-10 membered heterocycloalkyl)-C1-4 alkyl-, CN, OH, NH2, NO2, NHORc, ORc, SRc, C(O)Rc, C(O)NRcRc, C(O)ORc, OC(O)Rc, OC(O)NRcRc, C(═NRc)NRcRc, NRcC(═NRc)NRcRc, NHRc, NRcRc, NRcC(O)Rc, NRcC(O)ORc, NRcC(O)NRcRc, NRcS(O)Rc, NRcS(O)2Rc, NRcS(O)2NRcRc, S(O)Rc, S(O)NRcRc, S(O)2Rc and S(O)2NRcRc;
• wherein the C1-4 alkyl, C1-4 haloalkyl, C1-4 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-(5-10 membered heteroaryl)-C1-4 alkyl- and (4-10 membered heterocycloalkyl)-C1-4 alkyl- of Rb are each further optionally substituted with 1-3 independently selected Rd substituents;
• each Rc is independently selected from H, C1-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl- and (4-10 membered heterocycloalkyl)-C1-4 alkyl- of Rc are each optionally substituted with 1, 2, 3, 4, or 5 Rf substituents independently selected from C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, (4-10 membered heterocycloalkyl)-C1-4 alkyl-, halo, CN, NHORg, ORg, SRg, C(O)Rg, C(O)NRgRg, C(O)ORg, OC(O)Rg, OC(O)NRgRg, NHRg, NRgRg, NRgC(O)Rg, NRgC(O)NRgRg, NRgC(O)ORg, C(═NRg)NRgRg, NRgC(═NRg)NRgRg, S(O)Rg, S(O)NRgRg, S(O)2R, NRgS(O)2Rg, NRgS(O)2NRgRg, and S(O)2NRgRg;
• wherein the C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl- of Rf are each optionally substituted with 1, 2, 3, 4, or 5 Rn substituents independently selected from C1-4 alkyl, C1-4 haloalkyl, halo, CN, NHORo, ORo, SRo, C(O)Ro, C(O)NRoRo, C(O)ORo, OC(O)Ro, OC(O)NRoRo, NHRo, NRoRo, NRoC(O)Ro, NRoC(O)NRoRo, NRoC(O)ORo, C(═NR)NRoRo, NRoC(═NR)NRoRo, S(O)Ro, S(O)NRoRo, S(O)2R, NRoS(O)2Ro, NRoS(O)2NRoR, and S(O)2NRoRo;
• each Rg is independently selected from H, C1-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl- and (4-10 membered heterocycloalkyl)-C1-4 alkyl- of Rg are each optionally substituted with 1-3 independently selected Rp substituents;
• or any two Ra 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 Rh substituents independently selected from C1-6 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, 5-6 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl-, (5-6 membered heteroaryl)-C1-4 alkyl-, (4-7 membered heterocycloalkyl)-C1-4 alkyl-, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, halo, CN, ORi, SRi, NHORi, C(O)Ri, C(O)NRiRi, C(O)ORi, OC(O)Ri, OC(O)NRiRi, NHRi, NRiRi, NRiC(O)Ri, NRiC(O)NRiRi, NRiC(O)ORi, C(═NRi)NRiRi, NRiC(═NRi)NRiRi, S(O)Ri, S(O)NRiRi, S(O)2Ri, NRiS(O)2Ri, NR'S(O)2NRiRi, and S(O)2NRiRi, wherein the C1-6 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, 5-6 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl-, (5-6 membered heteroaryl)-C1-4 alkyl-, (4-7 membered heterocycloalkyl)-C1-4 alkyl- of Rh are each further optionally substituted by 1, 2, or 3 Rj substituents independently selected from C3-6 cycloalkyl, C6-10 aryl, 5 or 6-membered heteroaryl, C24 alkenyl, C24 alkynyl, halo, C1-4 alkyl, C1-4 haloalkyl, CN, NHORk, ORk, SRk, C(O)Rk, C(O)NRkRk, C(O)ORk, OC(O)Rk, OC(O)NRkRk, NHRk, NRkRk, NRkC(O)Rk, NRkC(O)NRkRk, NRkC(O)ORk, C(═NRk)NRkRk, NRkC(═NRk)NRkRk, S(O)Rk, S(O)NRkRk, S(O)2Rk, NRkS(O)2Rk, NRkS(O)2NRkRk, and S(O)2NRkRk;
• or two Rh 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 C3-6 cycloalkyl or 4- to 6-membered heterocycloalkyl having 1-2 heteroatoms as ring members selected from O, N or S;
• or any two Rc 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 Rh substituents;
• or any two Re 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 Rh substituents;
• or any two Rg 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 Rh substituents;
• or any two Ri 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 Rh substituents;
• or any two Rk 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 Rh substituents;
• or any two Ro 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 Rh substituents;
• and
• each Re, Ri, Rk, Ro or Rp is independently selected from H, C1-4 alkyl, C3-6 cycloalkyl, C6-10 aryl, 5 or 6-membered heteroaryl, C1-4 haloalkyl, C2-4 alkenyl, and C2-4 alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C6-10 aryl, 5 or 6-membered heteroaryl, C2-4 alkenyl, and C2-4 alkynyl of Re, Ri, Rk, Ro or Rp are each optionally substituted with 1, 2 or 3 Rq substituents;
• each Rq is independently selected from OH, CN, —COOH, NH2, halo, C1-6haloalkyl, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylthio, phenyl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, C3-6 cycloalkyl, NHR12, NR12R12, and C1-4 haloalkoxy, wherein the C1-6 alkyl, phenyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl of Rq are each optionally substituted with halo, OH, CN, —COOH, NH2, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, phenyl, C3-10 cycloalkyl and 4-6 membered heterocycloalkyl and each R12 is independently C1-6 alkyl;
• is a single bond or a double bond to maintain ring A being aromatic;
• the subscript n is an integer of 1, 2, 3, 4, 5 or 6;
• and
• when R9 is OH, Cy is other than 6-carbamimidoyl-1H-benzo[d]imidazol-2-yl.