Pyrrolo[2,3-b]pyridine cdk9 kinase inhibitors

A compound of formula (IIIa), or a pharmaceutically acceptable salt thereof,

• wherein
• one of X1, X2, X3, X4, and X5 is N;
• and the remaining are CR3A;
• or
• two of X1, X2, X3, X4, and X5 are N;
• and the remaining are CR3A;
• R1 is selected from the group consisting of cycloalkyl, cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl;
• wherein the R1 cycloalkyl, cycloalkenyl, heterocycloalkyl and heterocycloalkenyl are optionally substituted with one or more substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, SO2NHC(O)R5, SO2NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, SO2NHC(O)OR5, SO2NR5C(O)OR5, NHSO2NHC(O)OR5, NHSO2NR5C(O)OR5, NR5SO2NR5C(O)OR5, NR5SO2NHC(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, OC(O)NH2, OC(O)NHR5, OC(O)N(R5)2, OC(O)NHSO2R5, OC(O)NR5SO2R5, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, OSO2NH2, OSO2NHR5, OSO2N(R5)2, C(O)NHCN, C(O)NR5CN, S(O)(N)R5, S(O)(N)R5SO2R5, C(O)H, C(O)OH, (O), OH, CN, NO2, F, Cl, Br and I;
• R2 is selected from the group consisting of hydrogen, C1-C4 alkyl, NO2, CN, C(O)NH2, C(O)OR2A, F, Cl, Br, and I;
• R2A is selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
• R3A, at each occurrence, is each independently selected from the group consisting of H, R6, OR6, SR6, S(O)R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, C(O)H, C(O)OH, (O), OH, CN, NO2, F, Cl, Br and I;
• R4 is selected from the group consisting of R4A, OR4A, C(O)NH2, CN, F, Cl, Br, and I;
• R4A is selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
• R5, at each occurrence, is independently selected from the group consisting of C1-C8 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, heterocycloalkyl, heterocycloalkenyl, cycloalkyl, and cycloalkenyl;
• wherein each R5 C1-C8 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, B(OH)2, C(O)H, C(O)OH, OH, CN, NO2, F, Cl, Br and I;
• wherein each R5 aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocycloalkyl, and heterocycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, (O), OH, CN, NO2, F, Cl, Br and I;
• R6, at each occurrence, is independently selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, phenyl, heteroaryl, heterocycloalkyl, heterocycloalkenyl, cycloalkyl, and cycloalkenyl;
• wherein each R6 C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, OH, CN, NO2, F, Cl, Br and I;
• wherein each R6 phenyl, cycloalkyl, cycloalkenyl, heteroaryl, heterocycloalkyl, and heterocycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, (O), OH, CN, NO2, F, Cl, Br and I;
• R7, at each occurrence, is independently selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, heterocycloalkyl, heterocycloalkenyl, cycloalkyl, and cycloalkenyl;
• wherein each R7 C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R13, OR13, NH2, NHR13, N(R13)2, C(O)H, C(O)OH, OH, CN, NO2, F, Cl, Br and I;
• wherein each R7 aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocycloalkyl, and heterocycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R11, OR11, SR11, S(O)R11, SO2R11, C(O)R11, CO(O)R11, OC(O)R11, OC(O)OR11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, NHS(O)2R11, NR11S(O)2R11, NHC(O)OR11, NR11C(O)OR11, NHC(O)NH2, NHC(O)NHR11, NHC(O)N(R11)2, NR11C(O)NHR11, NR11C(O)N(R11)2, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)NHOH, C(O)NHOR11, C(O)NHSO2R11, C(O)NR11SO2R11, SO2NH2, SO2NHR11, SO2N(R11)2, C(O)H, C(O)OH, (O), OH, CN, NO2, F, Cl, Br and I;
• R8, at each occurrence, is independently selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, and heterocycloalkyl;
• wherein each R8 C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of aryl, heteroaryl, SO2R8A, C(O)OR8A, C(O)NH2, C(O)NHR8A, C(O)N(R8A)2, C(O)NHSO2R8A, C(O)NR8ASO2R8A, NH2, C(O)H, C(O)OH, OH, CN, NO2, F, Cl, Br and I;
• wherein each R8 heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of NH2, C(O)H, C(O)OH, OH, CN, NO2, F, Cl, Br and I;
• R8A, at each occurrence, is independently selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
• R9, at each occurrence, is independently selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, heterocycloalkyl, heterocycloalkenyl, cycloalkyl, and cycloalkenyl;
• wherein each R9 aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocycloalkyl, and heterocycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R12, OR12, SR12, S(O)R12, SO2R12, C(O)R12, CO(O)R12, OC(O)R12, OC(O)OR12, NH2, NHR12, N(R12)2, NHC(O)R12, NR12C(O)R12, NHS(O)2R12, NR12S(O)2R12, NHC(O)OR12, NR12C(O)OR12, NHC(O)NH2, NHC(O)NHR12, NHC(O)N(R12)2, NR12C(O)NHR12, NR12C(O)N(R12)2, C(O)NH2, C(O)NHR12, C(O)N(R12)2, C(O)NHOH, C(O)NHOR12, C(O)NHSO2R12, C(O)NR12SO2R12, SO2NH2, SO2NHR12, SO2N(R12)2, C(O)H, C(O)OH, (O), OH, CN, NO2, F, Cl, Br and I;
• R10, at each occurrence, is independently selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
• wherein each R10 C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of NH2, C(O)H, C(O)OH, OH, CN, NO2, F, Cl, Br and I;
• R11, at each occurrence, is independently selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, and heteroaryl;
• wherein each R11 C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of OR11A, NH2, NHR11A, N(R11A)2, C(O)H, C(O)OH, OH, CN, NO2, F, Cl, Br and I;
• wherein each R11 aryl and heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of C1-C6 alkyl, C1-C6 haloalkyl, NH2, C(O)H, C(O)OH, OH, CN, NO2, F, Cl, Br and I;
• R11A, at each occurrence, is independently selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
• R12, at each occurrence, is independently selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
• wherein each R12 C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of NH2, NHR14, N(R14)2, C(O)H, C(O)OH, OH, CN, NO2, F, Cl, Br and I;
• R13, at each occurrence, is independently selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, and heterocycloalkyl, heterocycloalkenyl;
• wherein each R13 C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R15, OR15, C(O)H, C(O)OH, OH, CN, NO2, F, Cl, Br and I;
• wherein each R13 aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocycloalkyl, and heterocycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R16, OR16, C(O)H, C(O)OH, (O), OH, CN, NO2, F, Cl, Br and I;
• R14, at each occurrence, is independently selected from the group consisting of C1-C6 haloalkyl, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
• R15, at each occurrence, is independently selected from the group consisting of C1-C6 haloalkyl, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
• wherein each R15 C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl is optionally substituted with one or more OCH3;
• and
• R16, at each occurrence, is independently selected from the group consisting of C1-C6 haloalkyl, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl.