Methods of use of diazacarbazoles for treating cancer

A method of inhibiting abnormal cell growth or treating a hyperproliferative disorder in a mammal comprising administering to said mammal a therapeutically effective amount of a compound of formula (I), or a salt thereof:

• X is CR2 or N;
• Y is CR4 or N;
• Z is CR8 or N;
• provided that no more than one of X, Y and Z is N at the same time;
• R2 is H, halo, CN, CF3, —OCF3, OH, —NO2, C1-C5 alkyl, —O(C1-C5 alkyl), —S(C1-C5 alkyl), or N(R22)2;
• R3 is H, halo, CN, —O—R9, —N(R22)—R9, —S(O)p—R9, or R9;
• p is 0, 1 or 2;
• R4 is H, halo, CN, CF3, —OCF3, OH, —NO2, —(CR14R15)nC(═Y)OR11, —(CR14R15)nC(═Y′)NR11R12, —(CR14R15)nNR11R12, —(CR14R15)nOR11, —(CR14R15)nS(O)pR11, —(CR14R15)nNR12C(═Y)R11, —(CR14R15)nNR12C(═Y′)OR11, —(CR14R15)nNR12C(═Y′)NR11R12, —(CR14R15)nNR12SO2R11, —(CR14R15)nOC(═Y′)R11, —(CR14R15)nOC(═Y′)NR11R12, —(CR14R15)—S(O)2NR11R12, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with one to four R13 groups;
• each n is independently 0-5;
• R5 is H, halo, CN, CF3, —OCF3, OH, —NO2, —(CR14R15)nC(═Y′)OR11, —(CR14R15)nC(═Y′)NR11R12, —(CR14R15)nNR12C(═Y)R11, —(CR14R15)nNR11R12, —(CR14R15)nOR11, —(CR14R15)nS(O)pR11, —(CR14R15)nNR12C(═Y′)OR11, —(CR14R15)nNR12C(═Y′)NR11R12—(CR14R15)nNR12SO2R11, —(CR14R15)nOC(═Y′)R11, —(CR14R15)nOC(═Y)NR11R12, —(CR14R15)nS(O)2NR11R12, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl wherein the said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with one to four R13 groups;
• R6 is CN, —CF3, —OCF3, halo, —C(═Y′)NR11R12, —OR11, —OC(═Y′)R11, —NR11R12, —NR12C(═Y′)R11, —NR12C(═Y′)NR11R12, —NR12S(O)qR11, —SR11, —S(O)R11, —S(O)2R11, —OC(═Y′)NR11R12, —S(O)2NR11R12, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted by one to four R13 groups;
• R8 is H, halo, CN, NO2, N(R22)2, OH, O(C1-C3 alkyl), or C1-C3 alkyl, wherein each said alkyl is optionally substituted with one to three fluoro groups;
• each R9 is independently alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each member of R9 is independently substituted with one to three R10 groups;
• each R10 is independently H, CN, —CF3, —OCF3, —NO2, halo, R11, —OR11, —NR12C(═Y′)R11, —NR12C(═NR12)R11, —NR12S(O)qR11, —SR11, —NR11R12, oxo, —C(═Y′)OR11, —C(═Y′)NR11R12, —S(O)qR11, —NR12C(═Y′)OR11, —NR12C(═Y′)NR11R12, —OC(═Y′)R11, —OC(═Y′)NR11R12, or —S(O)2NR11R12;
• each q independently is 1 or 2;
• R11 and R12 are independently H, alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with one to four R13 groups, wherein two geminal R13 groups are optionally taken together with the atom to which they are attached to form a 3-6 membered ring having additional 0-2 heteroatoms selected from O, S, and N, said ring being optionally substituted with one to four R18 groups;
• R11 and R12 are optionally taken together with the attached N atom to form a 4-7 membered ring having additional 0-2 heteroatoms selected from O, S, and N, said ring being optionally substituted with one to four R13 groups;
• each R13 is independently halo, CN, CF3, —OCF3, —NO2, oxo, —(CR14R15)nC(═Y′)R16, —(CR14R15)nC(═Y′)OR16, —(CR14R15)nC(═Y′)NR16R17, —(CR14R15)nNR16R17, —(CR14R15)nOR16, —(CR14R15)nSR16, —(CR14R15)nNR16C(═Y)R17, —(CR14R15)nNR16C(═Y′)OR17, —(CR14R15)nNR17C(═Y′)NR16R17, —(CR14R15)nNR17SO2R16, —(CR14R15)nOC(═Y′)R16, —(CR14R15)nOC(═Y)NR16R17, —(CR14R15)nS(O)R16, —(CR14R15)nS(O)2R16, —(CR14R15)nS(O)2NR16R17, or R16;
• R14 and R15 are independently selected from H, alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with one to four R18 groups;
• R16 and R17 are independently H, alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with one to four R18 groups;
• R16 and R17 are optionally taken together with the attached N atom to form a 5-6 membered ring having additional 0-2 heteroatoms selected from O, S, and N, said ring being optionally substituted with one to four R18 groups;
• each R18 is independently H, alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, CN, CF3, —OCF3, —NO2, oxo, —(CR19R20)nC(═Y′)R23, —(CR19R20)nC(═Y′)OR23, —(CR19R20)nC(═Y′)NR23R24, —(CR19R20)nNR23R24, —(CR19R20)nOR23, —(CR19R20)n—SR23, —(CR19R20)nNR24C(═Y′)R23, —(CR19R20)nNR24C(═Y′)OR23, —(CR19R20)nNR22C(═Y′)NR23R24, —(CR19R20)nNR24SO2R23, —(CR19R20)nOC(═Y′)R23, —(CR19R20)nOC(═Y′)NR23R24, —(CR19R20)nS(O)R23, —(CR19R20)nS(O)2R23, or —(CR19R20)nS(O)2NR23R24, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with one to four R21 groups;
• R19 and R20 are independently H, alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with one to four R25 groups;
• R23 and R24 are independently H, alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with one to four R21 groups;
• R23 and R24 are optionally taken together with the attached N atom to form a 5-6 membered ring having additional 0-2 heteroatoms selected from O, S, and N, said ring being optionally substituted with one to four R21 groups;
• each R21 is independently H, alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, CN, CF3, —OCF3, —NO2, oxo, —C(═Y)R25, —C(═Y′)OR25, —C(═Y′)NR25R26, —NR25R26, —OR25, —SR25, —NR26C(═Y′)R25, —NR26C(═Y′)OR25, —NR25R26, —NR26SO2R25, —OC(═Y′)R25, —OC(═Y′)NR25R26, —S(O)R25, —S(O)2R25, or —S(O)2NR25R26, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with one to four R25 groups;
• each R25 and R26 is independently H, alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one to four groups selected from halo, —CN, —OCF3, —CF3, —NO2, —C1-C6 alkyl, —OH, oxo, —SH, —O(C1-C6 alkyl), —S(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —SO2(C1-C6 alkyl), —CO2H, —CO2(C1-C6 alkyl), —C(O)NH2, —C(O)NH(C1-C6 alkyl), —C(O)N(C1-C6 alkyl)2, —N(C1-C6 alkyl)C(O)(C1-C6 alkyl), —NHC(O)(C1-C6 alkyl), —NHSO2(C1-C6 alkyl), —N(C1-C6 alkyl)SO2(C1-C6 alkyl), —SO2NH2, —SO2NH(C1-C6 alkyl), —SO2N(C1-C6 alkyl)2, —OC(O)NH2, —OC(O)NH(C1-C6 alkyl), —OC(O)N(C1-C6 alkyl)2, —NHC(O)NH(C1-C6 alkyl), —NHC(O)N(C1-C6 alkyl)2, —N(C1-C6 alkyl)C(O)NH(C1-C6 alkyl), —N(C1-C6 alkyl)C(O)N(C1-C6 alkyl)2, —NHC(O)NH(C1-C6 alkyl), —NHC(O)N(C1-C6 alkyl)2, —NHC(O)O(C1-C6 alkyl), and —N(C1-C6 alkyl)C(O)O(C1-C6 alkyl);
• R25 and R26 are optionally taken together with the attached N atom to form a 5-6 membered ring having additional 0-2 heteroatoms selected from O, S, and N, said ring being optionally substituted with one to four groups selected from halo, —CN, —OCF3, CF3, —NO2, —C1-C6 alkyl, —OH, oxo, —SH, —O(C1-C6 alkyl), —S(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —SO2(C1-C6 alkyl), —CO2H, —CO2(C1-C6 alkyl), —C(O)NH2, —C(O)NH(C1-C6 alkyl), —C(O)N(C1-C6 alkyl)2, —N(C1-C6 alkyl)C(O)(C1-C6 alkyl), —NHC(O)(C1-C6 alkyl), —NHSO2(C1-C6 alkyl), —N(C1-C6 alkyl)SO2(C1-C6 alkyl), —SO2NH2, —SO2NH(C1-C6 alkyl), —SO2N(C1-C6 alkyl)2, —OC(O)NH2, —OC(O)NH(C1-C6 alkyl), —OC(O)N(C1-C6 alkyl)2, —NHC(O)NH(C1-C6 alkyl), —NHC(O)N(C1-C6 alkyl)2, —N(C1-C6 alkyl)C(O)NH(C1-C6 alkyl), —N(C1-C6 alkyl)C(O)N(C1-C6 alkyl)2, —NHC(O)NH(C1-C6 alkyl), —NHC(O)N(C1-C6 alkyl)2, —NHC(O)O(C1-C6 alkyl), and —N(C1-C6 alkyl)C(O)O(C1-C6 alkyl);
• Y′ is independently O, NR22, or S;
• and
• each R22 is independently H or C1-C5 alkyl.