Substituted heterocycle fused gamma-carbolines

A compound of the formula (I)

• or stereoisomers or pharmaceutically acceptable salt forms thereof, wherein:
• b is a single bond;
• X is —NR10A—;
• R1 is selected from
• H,
• C(═O)R2,
• C(═O)OR2,
• C1-8 alkyl,
• C2-8 alkenyl,
• C2-8 alkynyl,
• C3-7 cycloalkyl,
• C1-6 alkyl substituted with Z,
• C2-6 alkenyl substituted with Z,
• C2-6 alkynyl substituted with Z,
• C3-6 cycloalkyl substituted with Z,
• aryl substituted with Z,
• 5-6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with Z;
• C1-3 alkyl substituted with Y,
• C2-3 alkenyl substituted with Y,
• C2-3 alkynyl substituted with Y,
• C1-6 alkyl substituted with 0-2 R2,
• C2-6 alkenyl substituted with 0-2 R2,
• C2-6 alkynyl substituted with 0-2 R2,
• aryl substituted with 0-2 R2, and
• 5-6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with 0-2 R2;
• Y is selected from
• C3-6 cycloalkyl substituted with Z,
• aryl substituted with Z,
• 5-6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with Z;
• C3-6 cycloalkyl substituted with —(C1-3 alkyl)-Z,
• aryl substituted with —(C1-3 alkyl)-Z, and
• 5-6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with —(C1-3 alkyl)-Z;
• Z is selected from H,
• —CH(OH)R2,
• —C(ethylenedioxy)R2,
• —OR2,
• —SR2,
• —NR2R3,
• —C(O)R2,
• —C(O)NR2R3,
• —NR3C(O)R2,
• —C(O)OR2,
• —OC(O) R2,
• —CH(═NR4)NR2R3,
• —NHC(═NR4)NR2R3,
• —S(O)R2,
• —S(O)2R2,
• —S(O)2NR2R3, and —NR3S(O)2R2;
• R2, at each occurrence, is independently selected from
• halo,
• C1-3 haloalkyl,
• C1-4 alkyl,
• C2-4 alkenyl,
• C2-4 alkynyl,
• C3-6 cycloalkyl,
• aryl substituted with 0-5 R42;
• C3-10 carbocyclic group substituted with 0-3 R41, and
• 5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R41;
• R3, at each occurrence, is independently selected from
• H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, and
• C1-4 alkoxy;
• alternatively, R2 and R3 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R4)—;
• R4, at each occurrence, is independently selected from H and C1-4 alkyl;
• R5 is H or C1-4 alkyl;
• R6a and R6b, at each occurrence, are independently selected from
• H, —OH, —NR46R47, —CF3, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, C3-6 cycloalkyl, and
• aryl substituted with 0-3 R44;
• R7 and R9, at each occurrence, are independently selected from
• H, halo, —CF3, —OCF3, —OH, —CN, —NO2, —NR46R47,
• C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-4 haloalkyl, C1-8 alkoxy, (C1-4 haloalkyl)oxy,
• C3-10 cycloalkyl substituted with 0-2 R33,
• C1-4 alkyl substituted with 0-2 R11,
• C3-10 carbocyclic group substituted with 0-3 R33,
• aryl substituted with 0-5 R33,
• 5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R31;
• OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═NR14)NR12R13, NHC(═NR14)NR12R13, S(O)R12, S(O)2R12, S(O)NR12R13, S(O)2NR12R13, NR14S(O)R12, NR14S(O)2R12, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O) NHR15;
• R8 is selected from
• H, halo, —CF3, —OCF3, —OH, —CN, —NO2,
• C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-4 haloalkyl, C1-8 alkoxy, (C1-4 haloalkyl)oxy,
• C3-10 cycloalkyl substituted with 0-2 R33,
• C1-4 alkyl substituted with 0-2 R11,
• C2-4 alkenyl substituted with 0-2 R11,
• C2-4 alkynyl substituted with 0-1 R11,
• C3-10 carbocyclic group substituted with 0-3 R33,
• aryl substituted with 0-5 R33,
• 5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R31;
• OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═NR14)NR12R13, NHC(═NR14)NR12R13, S(O)R12, S(O)2R12, S(O) NR12R13, S(O)2NR12R13, NR14S(O)R12, NR14S(O)2R12, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
• R10A is selected from H,
• C1-6 alkyl substituted with 0-1 R10B,
• C2-6 alkenyl substituted with 0-1 R10B,
• C2-6 alkynyl substituted with 0-1 R10, and
• C16 alkoxy;
• R10B is selected from
• C1-4 alkoxy,
• C3-6 cycloalkyl,
• C3-10 carbocyclic group substituted with 0-3 R33,
• phenyl substituted with 0-3 R33, and
• 5-6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R44;
• R11 is selected from
• H, halo, —CF3, —CN, —NO2,
• C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-4 haloalkyl, C1-8 alkoxy, C3-10 cycloalkyl,
• C3-10 carbocyclic group substituted with 0-3 R33,
• aryl substituted with 0-5 R33,
• 5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R31;
• OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═NR14)NR12R13, NHC(═NR14)NR12R13, S(O)R12, S(O)2R12, S(O) NR12R13, S(O)2NR12R13, NR14S(O)R12, NR14S(O)2R12, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O) NHR15;
• R12, at each occurrence, is independently selected from
• C1-4 alkyl substituted with 0-1 R12a,
• C2-4 alkenyl substituted with 0-1 R12a,
• C2-4 alkynyl substituted with 0-1 R12a,
• C3-6 cycloalkyl substituted with 0-3 R33,
• phenyl substituted with 0-5 R33;
• C3-10 carbocyclic group substituted with 0-3 R33, and
• 5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R31;
• R12a, at each occurrence, is independently selected from
• phenyl substituted with 0-5 R33;
• C3-10 carbocyclic group substituted with 0-3 R33, and
• 5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R31;
• R13, at each occurrence, is independently selected from
• H, C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl;
• alternatively, R12 and R13 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R14)—;
• alternatively, R12 and R13 when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1-3 heteroatoms selected from the group consisting of N, O, and S, wherein said bicyclic heterocyclic ring system is unsaturated or partially saturated, wherein said bicyclic heterocyclic ring system is substituted with 0-3 R16;
• R14, at each occurrence, is independently selected from H 12 and C1-4 alkyl;
• R15, at each occurrence, is independently selected from
• H, C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl;
• R16, at each occurrence, is independently selected from
• H, OH, halo, CN, NO2, CF3, SO2R45, NR46R47, —C(═O)H,
• C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl,
• C1-3 haloalkyl-oxy-, and C1-3 alkyloxy-;
• R31, at each occurrence, is independently selected from
• H, OH, halo, CF3, SO2R45, NR46R47, and C1-4 alkyl;
• R33, at each occurrence, is independently selected from
• H, OH, halo, CN, NO2, CF3, SO2R45, NR46R47, —C(═O)H,
• C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl,
• C3-6 cycloalkyl, C1-4 haloalkyl, C1-4 haloalkyl-oxy-,
• C1-4 alkyloxy-,
• C1-4 alkylthio-, C1-4 alkyl-C(═O)—, C1-4 alkyl-C(═O)NH—,
• C1-4 alkyl-OC(═O)—,
• C1-4 alkyl-C(═O)O—, C3-6 cycloalkyl-oxy-, C3-6 cycloalkylmethyl-oxy-;
• C1-6 alkyl substituted with OH, methoxy, ethoxy,
• propoxy, or butoxy;
• and
• C2-6 alkenyl substituted with OH, methoxy, ethoxy,
• propoxy, or butoxy;
• R41, at each occurrence, is independently selected from
• H, CF3, halo, OH, —CO2H, SO2R45, NR46R47, NO2, CN, ═O;
• C2-8 alkenyl, C2-8 alkynyl, C1-4 alkoxy, C1-4 haloalkyl
• C1-4 alkyl substituted with 0-1 R43,
• aryl substituted with 0-3 R42, and
• 5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R44;
• R42, at each occurrence, is independently selected from
• H, CF3, halo, OH, CO2H, SO2R45, SOR45, SR45, NR46SO2R45, NR46COR45, NR46R47, NO2, CN, CH(═NH)NH2, NHC(═NH)NH2,
• C2-6 alkenyl, C2-6 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, C3-6 cycloalkyl,
• C1-4 alkyl substituted with 0-1 R43,
• aryl substituted with 0-3 R44, and
• 5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R44;
• R43 is C3-6 cycloalkyl or aryl substituted with 0-3 R44;
• R44, at each occurrence, is independently selected from H,
• halo, —OH, NR46R47, CO2H, SO2R45, —CF3, —OCF3, —CN, —NO2,
• C1-4 alkyl, and C1-4 alkoxy;
• R45 is C1-4 alkyl;
• R46, at each occurrence, is independently selected from H and C1-4 alkyl;
• R47, at each occurrence, is independently selected from H,
• C1-4 alkyl, —C(═O)NH(C1-4 alkyl), —SO2 (C1-4 alkyl),
• —C(═O)O(C1-4 alkyl), —C(═O) (C1-4 alkyl), and —C(═O)H;
• k is 1 or 2;
• m is 0, 1, or 2;
• and
• n is 1, 2, or 3;
• provided when m is 0 or 1 then k is 1 or 2;
• provided when m is 2 then k is 1.