Bicyclic inhibitors of alk

A compound of formula (I):

• X is CH or N;
• Y is CH or N;
• wherein at least one of X and Y is N;
• A is phenyl, naphthyl, indenyl, C3-8 cycloalkyl, 4-7 membered heterocycloalkyl, 5-7 membered heterocycloalkenyl, or 5-7 membered heteroaryl;
• B is
• (a) phenyl, naphthyl, tetrahydronaphthyl, indenyl, or indanyl, wherein the phenyl, naphthyl, tetrahydronaphthyl, indenyl, or indanyl is optionally substituted with one, two, three, or four R2 and is substituted with R3;
• or
• (b) 5-16 membered monocyclic, bicyclic, or tricyclic heterocyclyl, wherein the heterocyclyl is optionally substituted with one, two, three, four, or five R4;
• Z is a bond, C1-6 alkylene, C2-6 alkenylene, —O— or —NR5—;
• R1, at each occurrence, is independently selected from the group consisting of halo, CN, NO2, C1-6-alkyl, C1-6-haloalkyl, aryl, C3-8 cycloalkyl, heteroaryl, heterocycloalkyl, OR6, SR6, C(O)R6, C(O)NR7R8, C(O)OR6, OC(O)R6, OC(O)NR7R8, NR7R8, NR7C(O)R6, S(O)R6, S(O)NR7R8, S(O)2R6, NR7S(O)2R6, and S(O)2NR7R8;
• wherein the C3-8 cycloalkyl, aryl, heterocycloalkyl, and heteroaryl are optionally substituted with 1, 2, or 3 substituents independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, CN, NO2, ORa, SRa, C(O)Ra, C(O)NRbRc, C(O)ORa, OC(O)Ra, OC(O)NRbRc, NRbRc, NRbC(O)Ra, S(O)Ra, S(O)NRbRc, S(O)2Ra, NRbS(O)2Ra, and S(O)2NRbRc;
• R2, at each occurrence, is independently selected from the group consisting of halo, CN, OH, C1-6 alkyl, C1-6-haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6-thioalkoxy, amino, C1-6 alkylamino, and C1-6 dialkylamino;
• R3 is selected from the group consisting of aryl, C3-8 cycloalkyl, heteroaryl, heterocycloalkyl, aryl-C1-6-alkyl-, C3-8 cycloalkyl-C1-6-alkyl-, heteroaryl-C1-6-alkyl-, heterocycloalkyl-C1-6-alkyl-, OR9, C(O)R9, —C1-6-alkyl-C(O)R9, C(O)NR10R11, C(O)OR9, OC(O)R9, OC(O)NR10R11, NR10R11, NR10C(O)R9, S(O)R9, S(O)NR10R11, S(O)2R9, NR10S(O)2R9, and S(O)2NR10R11, wherein the C3-8 cycloalkyl, aryl, heterocycloalkyl, and heteroaryl, alone or part of another moiety, are optionally substituted with one, two, or three R12;
• R4 is CN, NO2, halo, C1-6-alkyl, C1-6-haloalkyl, ORj, SRj, C(O)Rd, C(O)NReRf, C(O)ORd, NReRf, NReC(O)Rd, S(O)2Rd, NReS(O)2Rd, or S(O)2NReRf;
• R5 is H or C1-6-alkyl;
• R6, R7, and R8, at each occurrence, are independently selected from H, C1-6 alkyl, C1-6 haloalkyl, aryl, C3-8 cycloalkyl, heteroaryl, and heterocycloalkyl, wherein the aryl, C3-8 cycloalkyl, heteroaryl, and heterocycloalkyl moiety are optionally substituted with 1, 2, or 3 substituents independently selected from halo, CN, OH, C1-6 alkyl, C1-6-haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, C1-6 dialkylamino, C(O)OH, C(O)C1-6 alkyl, C(O)NH2, C(O)NH(C1-6 alkyl), or C(O)N(C1-6 alkyl)2;
• R9, R10, and R11, at each occurrence, are independently selected from H, C1-6 alkyl, C1-6 haloalkyl, heteroaryl-C1-6-alkyl-, heterocycloalkyl-C1-6-alkyl-, R13R14N—C1-6-alkyl-, aryl, C3-8 cycloalkyl, heteroaryl, and heterocycloalkyl, wherein the aryl, C3-8 cycloalkyl, heteroaryl, and heterocycloalkyl, alone or as part of another moiety, are optionally substituted with 1, 2, or 3 substituents independently selected from halo, CN, OH, C1-6 alkyl, C1-6-haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, C1-6 dialkylamino, C(O)OH, C(O)C1-6 alkyl, C(O)NH2, C(O)NH(C1-6 alkyl), or C(O)N(C1-6 alkyl)2;
• R12, at each occurrence, is independently selected from the group consisting of halo, C1-6 alkyl, C1-6 haloalkyl, amino-C1-6-alkyl-, C1-6 alkylamino-C1-6 alkyl-, C1-6 dialkylamino-C1-6 alkyl-, hydroxy-C1-6-alkyl-, C1-6 alkyl-C1-6 alkoxy, aryl, C3-8 cycloalkyl, heteroaryl, heterocycloalkyl, aryl-(C1-6 alkyl)-, C3-8 cycloalkyl-(C1-6 alkyl)-, heteroaryl-(C1-6 alkyl)-, heterocycloalkyl-(C1-6 alkyl)-, CN, NO2, ORg, SRg, C(O)Rg, C(O)NRhRi, C(O)ORg, OC(O)Rg, OC(O)NRhRi, NRhRi, NRhC(O)Rg, S(O)Rg, S(O)NRhRi, S(O)2Rg, NRhS(O)2Rg, and S(O)2NRhRi, wherein the aryl, C3-8 cycloalkyl, heteroaryl, and heterocycloalkyl, alone or as part of another moiety, are optionally substituted with one, two or three substituents independently selected from halo and C1-6 alkyl;
• R13 and R14, at each occurrence, are independently selected from the group consisting of H, C1-6 alkyl, aryl, C3-8 cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the C1-6-alkyl is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, C1-6-alkoxy, —NH2, —NHC1-6-alkyl, and —N(C1-6-alkyl)2, and wherein the aryl, C3-8 cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted with one or more substituents selected from the group consisting of halo, C1-6-alkyl, C1-6-haloalkyl, C1-6-hydroxyalkyl, hydroxy, oxo, C1-6-alkoxy, C1-6-haloalkoxy, —NH2, —NH(C1-6-alkyl), and N(C1-6-alkyl)2;
• Ra, at each occurrence, is independently selected from the group consisting of H, C1-6 alkyl, aryl, C3-8 cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the C1-6-alkyl is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, C1-6-alkoxy, —NH2, —NHC1-6-alkyl, and —N(C1-6-alkyl)2, and wherein the aryl, C3-8 cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted with one or more substituents selected from the group consisting of halo, C1-6-alkyl, C1-6-haloalkyl, C1-6-hydroxyalkyl, hydroxy, oxo, C1-6-alkoxy, C1-6-haloalkoxy, —NH2, —NH(C1-6-alkyl), and N(C1-6-alkyl)2;
• Rb and Rc, at each occurrence, are independently selected from the group consisting of H, C1-6 alkyl, aryl, C3-8 cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the C1-6-alkyl is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, C1-6-alkoxy, —NH2, —NHC1-6-alkyl, and —N(C1-6-alkyl)2, and wherein the aryl, C3-8 cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted with one or more substituents selected from the group consisting of halo, C1-6-alkyl, C1-6-haloalkyl, C1-6-hydroxyalkyl, hydroxy, oxo, C1-6-alkoxy, C1-6-haloalkoxy, —NH2, —NH(C1-6-alkyl), and N(C1-6-alkyl)2;
• Rd, at each occurrence, is independently selected from the group consisting of H, C1-6 alkyl, aryl, C3-8 cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the C1-6-alkyl is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, C1-6-alkoxy, —NH2, —NHC1-6-alkyl, and —N(C1-6-alkyl)2, and wherein the aryl, C3-8 cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted with one or more substituents selected from the group consisting of halo, C1-6-alkyl, C1-6-haloalkyl, C1-6-hydroxyalkyl, hydroxy, oxo, C1-6-alkoxy, C1-6-haloalkoxy, —NH2, —NH(C1-6-alkyl), and N(C1-6-alkyl)2;
• Re and Rf, at each occurrence, are independently selected from the group consisting of H, C1-6 alkyl, aryl, C3-8 cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the C1-6-alkyl is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, C1-6-alkoxy, —NH2, —NHC1-6-alkyl, and —N(C1-6-alkyl)2, and wherein the aryl, C3-8 cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted with one or more substituents selected from the group consisting of halo, C1-6-alkyl, C1-6-haloalkyl, C1-6-hydroxyalkyl, hydroxy, oxo, C1-6-alkoxy, C1-6-haloalkoxy, —NH2, —NH(C1-6-alkyl), and N(C1-6-alkyl)2;
• Rg, at each occurrence, is independently selected from the group consisting of H, C1-6 alkyl, aryl, C3-8 cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the C1-6-alkyl is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, C1-6-alkoxy, —NH2, —NHC1-6-alkyl, and —N(C1-6-alkyl)2, and wherein the aryl, C3-8 cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted with one or more substituents selected from the group consisting of halo, C1-6-alkyl, C1-6-haloalkyl, C1-6-hydroxyalkyl, hydroxy, oxo, C1-6-alkoxy, C1-6-haloalkoxy, —NH2, —NH(C1-6-alkyl), and N(C1-6-alkyl)2;
• Rh and Ri, at each occurrence, are independently selected from the group consisting of H, C1-6 alkyl, aryl, C3-8 cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the C1-6-alkyl is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, C1-6-alkoxy, —NH2, —NHC1-6-alkyl, and —N(C1-6-alkyl)2, and wherein the aryl, C3-8 cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted with one or more substituents selected from the group consisting of halo, C1-6-alkyl, C1-6-haloalkyl, C1-6-hydroxyalkyl, hydroxy, oxo, C1-6-alkoxy, C1-6-haloalkoxy, —NH2, —NH(C1-6-alkyl), and N(C1-6-alkyl)2;
• and
• n is 0, 1, 2, or 3;
• or a pharmaceutically acceptable salt or solvate thereof.