Bicyclic carboxamide inhibitors of kinases

A compound of formula (I):

• wherein
• X2 is N, X5 is C, X1, X3, and X4 are CH;
• or
• X1 and X2 are N, X5 is C, and X3 and X4 are CR14;
• or
• X1 and X3 are N, X2 and X5 are C, and X4 is CR14;
• or
• X1, X2, and X4 are N, X5 is C, and X3 is CR14;
• or
• X1, X2, X3, and X4 are N and X5 is C;
• or
• X1 and X5 are N, X2 is C, and X3 and X4 are CH;
• A is phenyl, naphthyl, indenyl, C3-8 cycloalkyl, 5-7 membered heterocycloalkyl, 5-7 membered heterocycloalkenyl, or 5-7 membered heteroaryl;
• B is phenyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, or pyrazolinyl, wherein B is optionally substituted with one, two, three, or four R2 and is substituted with R3;
• or
• B is 1,2,3,4-tetrahydroisoquinoline;
• Z is a bond, C1-6 alkylene, or C2-6 alkenylene;
• 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, OR5, SR5, C(O)R5, C(O)NR6R7, C(O)OR5, OC(O)R5, OC(O)NR6R7, NR6R7, NR6C(O)R5, S(O)R5, S(O)NR6R7, S(O)2R5, NR6S(O)2R5, and S(O)2NR6R7;
• wherein the C3-8 cycloalkyl, aryl, heterocycloalkyl, and heteroaryl are optionally substituted with 1, 2, or 3 substituents independently selected from halo, C1-4 alkyl, C1-4 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, C1-4 alkyl, C1-4-haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, C1-4-thioalkoxy, —S(O)C1-4 alkyl;
• amino, C1-4 alkylamino, and C1-4 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-, OR8, C(O)R8, —CH2C(O)R8, C(O)NR9R10, C(O)OR8, OC(O)R8, OC(O)NR9R10, NR9R10, NR9C(O)R8, S(O)R8, S(O)NR9R10, S(O)2R8, NR9S(O)2R8, and S(O)2NR9R10, wherein the C3-8 cycloalkyl, aryl, heterocycloalkyl, and heteroaryl, alone or part of another moiety, are optionally substituted with one, two, or three R11;
• R4 is H or C1-6-alkyl;
• R5, R6, and R7, 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, C1-4 alkyl, C1-4-haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-4 alkylamino, C1-4 dialkylamino, C(O)OH, C(O)C1-4 alkyl, C(O)NH2, C(O)NH(C1-4 alkyl), or C(O)N(C1-4 alkyl)2;
• R8, R9, and R10, at each occurrence, are independently selected from H, C1-6 alkyl, C1-6 haloalkyl, heteroaryl-C1-6-alkyl-, heterocycloalkyl-C1-6-alkyl-, R12R13N—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, C1-4 alkyl, C1-4-haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-4 alkylamino, C1-4 dialkylamino, C(O)OH, C(O)C1-4 alkyl, C(O)NH2, C(O)NH(C1-4 alkyl), or C(O)N(C1-4 alkyl)2;
• R11, at each occurrence, is independently selected from the group consisting of halo, C1-4 alkyl, C1-4 haloalkyl, amino-C1-4-alkyl-, C1-4 alkylamino-C1-4 alkyl-, C1-4 dialkylamino-C1-4 alkyl-, hydroxy-C1-4-alkyl-, C1-4 alkyl-C1-4 alkoxy, aryl, C3-8 cycloalkyl, heteroaryl, heterocycloalkyl, aryl-(C1-2 alkyl)-, C3-8 cycloalkyl-(C1-2 alkyl)-, heteroaryl-(C1-2 alkyl)-, heterocycloalkyl-(C1-2 alkyl)-, CN, NO2, ORd, SRd, C(O)Rd, C(O)NReRf, C(O)ORd, OC(O)Rd, OC(O)NReRf, NReRf, NReC(O)Rd, S(O)Rd, S(O)NReRf, S(O)2Rd, NReS(O)2Rd, and S(O)2NReRf, 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 C1-4 alkyl;
• R12 and R13, at each occurrence, are independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, aryl, C3-8 cycloalkyl, heteroaryl, and heterocycloalkyl;
• R14 is selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, —C1-6 alkyl-heterocycloalkyl, —C(O)OC1-6 alkyl, —C(O)OC1-6 haloalkyl, —C(O)NHC1-6 alkyl, —C(O)NHC1-6 haloalkyl;
• Ra, at each occurrence, is independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, aryl, C3-8 cycloalkyl, heteroaryl, and heterocycloalkyl;
• Rb and Rc, at each occurrence, are independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, aryl, C3-8 cycloalkyl, heteroaryl, heterocycloalkyl;
• Rd, at each occurrence, is independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, aryl, C3-8 cycloalkyl, heteroaryl, and heterocycloalkyl;
• Re and Rf, at each occurrence, are independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, aryl, C3-8 cycloalkyl, heteroaryl, and heterocycloalkyl;
• and
• n is 0, 1, 2, or 3;
• or a pharmaceutically acceptable salt or solvate thereof.