Phthalazin-(2h)-one inhibitors of kinases

A compound having formula (I)

• wherein
• R1a, R1b, and R1c are independently hydrogen, hydroxy, nitro, halogen, cyano, trifluoromethyl, trifluoromethoxy, C1-4-alkyl, —ORa, or —NRbRc;
• X is heteroaryl, which is optionally substituted with one or more R5;
• n is 0, 1, 2, or 3;
• provided that when n is 1, 2, or 3, m is 0;
• m is 0, 1, 2, or 3;
• provided that when m is 1, 2, or 3, n is 0;
• Y is a bond, —O—, —C(O)—, —(O)C—, —C(O)O—, —OC(O)—, —NRe—, —NReC(O)—, —C(O)NRe—, —NReC(O)NRf—, —SO2NRe—, or —NReSO2—;
• Z is C3-8-cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein the C3-8-cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one or more R6;
• R5 is selected from the group consisting of C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, halogen, oxo, cyano, nitro, —ORd, —C(O)Rd, —C(O)ORd, —OC(O)Rd, —NReRf, —NReC(O)Rd, —NHC(O)NHRe, —NHSO2Rd, —C(O)NReRf, —SRd, —S(O)Rd, —SO2Rd, —SO2NReNRf, —B(OH)2, —CF3, —CF2CF3, —OCF3, and —OCF2CF3 wherein (a) the R5 C1-8-alkyl, C2-8-alkenyl, and C2-8-alkynyl, substituents are optionally substituted with one or more substituents selected from the group consisting of aryl, heterocyclyl, C3-8-cycloalkyl, halogen, cyano, nitro, oxo, —ORg, —C(O)Rg, —C(O)ORg, —OC(O)Rg, —NRhRi, —NRhC(O)g, —NHSO2Rg, —NHC(O)NHRh, —C(O)NRhRi;
• and wherein (b) the R5 aryl and heterocyclyl substituents are optionally substituted with one or more substituents independently selected from the group consisting of C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, halogen, cyano, nitro, oxo —ORj, —C(O)Rj, —C(O)ORj, —OC(O)Rj, —NRkRl, —NRkC(O)Rj, —NHC(O)NHRk, —NHSO2Rj, —C(O)NRkRl, —SRj, —S(O)Rj, —SO2Rj, —SO2NRkNRl, —CF3, —CF2CF3, —OCF3, and —OCF2CF3;
• R6 is selected from the group consisting of C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, halogen, oxo, cyano, nitro, —ORd, —C(O)Rd, —C(O)ORd, —OC(O)Rd, —NReRf, —NReC(O)Rd, —NHC(O)NHRe, —NHSO2Rd, —C(O)NReRf, —SRd, —S(O)Rd, —SO2Rd, —SO2NReNRf, —B(OH)2, —CF3, —CF2CF3, —OCF3, and —OCF2CF3 wherein (a) the R6 C1-8-alkyl, C2-8-alkenyl, and C2-8-alkynyl, substituents are optionally substituted with one or more substituents selected from the group consisting of aryl, heterocyclyl, C3-8-cycloalkyl, halogen, cyano, nitro, oxo, —ORg, —C(O)Rg, —C(O)ORg, —OC(O)Rg, —NRhRi, —NRhC(O)Rg, —NHSO2Rg, —NHC(O)NHRh, —C(O)NRhRi;
• and wherein (b) the R6 aryl and heterocyclyl substituents are optionally substituted with one or more substituents independently selected from the group consisting of C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, halogen, cyano, nitro, oxo —ORj, —C(O)Rj, —C(O)ORj, —OC(O)Rj, —NRkRl, —NRkC(O)Rj, —NHC(O)NHRk, —NHSO2Rj, —C(O)NRkRl, —SRj, —S(O)Rj, —SO2Rj, —SO2NRkNRl, —CF3, —CF2CF3, —OCF3, and —OCF2CF3;
• Ra, at each occurrence, is selected from the group consisting of hydrogen, C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, and C3-8-cycloalkyl, wherein the C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, and C3-8-cycloalkyl are optionally substituted with one or more substituents independently selected from the group consisting of C1-8-alkyl, aryl, heterocyclyl, C3-8-cycloalkyl, halogen, cyano, oxo, hydroxy, C1-8-alkoxy, —NH2, —NH(C1-8-alkyl), —O(C1-8-alkyl)NH2, and —N(C1-8-alkyl)2;
• Rb and Rc, at each occurrence, are independently selected from the group consisting of hydrogen, C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, and C3-8-cycloalkyl, and optionally, Rb and Rc can be joined together to form a 4-7 membered heterocycloalkyl ring, wherein the C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, C3-8-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionally substituted with one or more substituents independently selected from the group consisting of C1-8-alkyl, aryl, heterocyclyl, C3-8-cycloalkyl, halogen, cyano, oxo, hydroxy, C1-8-alkoxy, —NH2, —NH(C1-8-alkyl), and —N(C1-8-alkyl)2;
• Rd, at each occurrence, is selected from the group consisting of hydrogen, C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, and C3-8-cycloalkyl, wherein the C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, and C3-8-cycloalkyl are optionally substituted with one or more substituents independently selected from the group consisting of C1-8-alkyl, aryl, aryl-(C1-8-alkyl)-, heterocyclyl, C3-8-cycloalkyl, halogen, cyano, oxo, hydroxy, C1-8-alkoxy, —NH2, —NH(C1-8-alkyl), and —N(C1-8-alkyl)2;
• wherein the aryl, aryl-(C1-8-alkyl)-, heterocyclyl, and C3-8-cycloalkyl, alone or as part of another group, are optionally substituted with one or more substituents independently selected from the group consisting of C1-8-alkyl, aryl, heterocyclyl, C3-8-cycloalkyl, halogen, cyano, oxo, hydroxy, C1-8-alkoxy, —NH2, —NH(C1-8-alkyl), and —N(C1-8-alkyl)2;
• Re and Rf, at each occurrence, are independently selected from the group consisting of hydrogen, C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, and C3-8-cycloalkyl, and optionally, Re and Rf can be joined together to form a 4-7 membered heterocycloalkyl ring, wherein the C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, C3-8-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionally substituted with one or more substituents independently selected from the group consisting of C1-8-alkyl, aryl, heterocyclyl, C3-8-cycloalkyl, halogen, cyano, oxo, hydroxy, C1-8-alkoxy, —NH2, —NH(C1-8-alkyl), and —N(C1-8-alkyl)2;
• Rg, at each occurrence, is selected from the group consisting of hydrogen, C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, and C3-8-cycloalkyl, wherein the C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, and C3-8-cycloalkyl are optionally substituted with one or more substituents independently selected from the group consisting of C1-8-alkyl, aryl, heterocyclyl, C3-8-cycloalkyl, halogen, cyano, oxo, hydroxy, C1-8-alkoxy, —NH2, —NH(C1-8-alkyl), and —N(C1-8-alkyl)2;
• Rh and Ri, at each occurrence, are independently selected from the group consisting of hydrogen, C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, and C3-8-cycloalkyl, and optionally, Rh and Ri can be joined together to form a 4-7 membered heterocycloalkyl ring, wherein the C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, C3-8-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionally substituted with one or more substituents independently selected from the group consisting of C1-8-alkyl, aryl, heterocyclyl, C3-8-cycloalkyl, halogen, cyano, oxo, hydroxy, C1-8-alkoxy, —NH2, —NH(C1-8-alkyl), and —N(C1-8-alkyl)2;
• Rj, at each occurrence, is selected from the group consisting of hydrogen, C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, and C3-8-cycloalkyl, wherein the C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, and C3-8-cycloalkyl are optionally substituted with one or more substituents independently selected from the group consisting of C1-8-alkyl, aryl, heterocyclyl, C3-8-cycloalkyl, halogen, cyano, oxo, hydroxy, C1-8-alkoxy, —NH2, —NH(C1-8-alkyl), and —N(C1-8-alkyl)2;
• Rk and Rl, at each occurrence, are independently selected from the group consisting of hydrogen, C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, and C3-8-cycloalkyl, and optionally, Rk and Rl can be joined together to form a 4-7 membered heterocycloalkyl ring, wherein the C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, aryl, heterocyclyl, C3-8-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionally substituted with one or more substituents independently selected from the group consisting of C1-8-alkyl, aryl, heterocyclyl, C3-8-cycloalkyl, halogen, cyano, oxo, hydroxy, C1-8-alkoxy, —NH2, —NH(C1-8-alkyl), and —N(C1-8-alkyl)2;
• or a pharmaceutically acceptable salt thereof.