Macrocycle complement factor b inhibitors

A compound of the formula (I), (IV), (V), or (VI):

• or a pharmaceutically acceptable salt thereof, wherein
• ring A represents a phenyl or a naphthyl ring;
• ring B and ring C form a bicyclic heteroaryl, bicyclic heterocyclyl, or bicyclic cycloalkyl moiety, where ring B is a monocyclic heteroaryl, monocyclic heterocyclyl, or monocyclic cycloalkyl ring, and ring C is a phenyl or monocyclic 6-membered heteroaryl ring;
• m is an integer 0, 1, 2, or 3;
• n is an integer 0, 1, or 2;
• R1 is independently selected from halogen, —NO2, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, hydroxy(C1-C6 alkyl), hydroxy(C1-C6 alkoxy), alkoxy(C1-C6 alkyl), alkoxy(C1-C6 alkoxy), and amino(C1-C6 alkyl);
• or
• R2 is independently selected from halogen, —CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy;
• R3 is selected from halogen, —CO2H, —CO2(C1-C6 alkyl), —CO(C1-C6 alkyl), —CONH2, —CONH(C1-C6 alkyl), —CON(C1-C6 alkyl)2, —CONH—OH, —CONH—OCO(C1-C6 alkyl), —CONH—NH2, —CONH—S(O)2R5, —SO2OH, —SO2(C1-C6 alkyl), —SO2N(R5)2, —SO2NH—COCH3, —S(O)(NR5)R5, —NH—SO2R5, —NHCO—NHSO2R5, —PO(OH)2, —PO(OH)R5, pyrazolyl, and tetrazolyl, wherein
• each R5 is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl optionally substituted with C1-C4 alkyl, and phenyl, and monocyclic heteroaryl;
• and
• X is CH2, CH, O, S, or NH, and Y is O, S, or NH, where X and Y, together with the atoms to which they are attached, form a 10- to 16-member macrocycle, the macrocycle optionally substituted with one or more R4, wherein
• each R4 is independently selected from the group consisting of halogen, —NO2, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, hydroxy(C1-C6 alkyl), hydroxy(C1-C6 alkoxy), alkoxy(C1-C6 alkyl), alkoxy(C1-C6 alkoxy), and amino(C1-C6 alkyl),
• or two R4 groups, together with the carbon to which they are attached, form a ═O;
• ring A2 represents a phenyl or a naphthyl ring;
• ring B2 and ring C2 form a bicyclic heteroaryl, bicyclic heterocyclyl, or bicyclic cycloalkyl moiety, where ring B2 is a monocyclic heteroaryl, monocyclic heterocyclyl, or monocyclic cycloalkyl ring, and ring C2 is a phenyl or monocyclic 6-membered heteroaryl ring;
• s is an integer 0, 1, or 2;
• t is an integer 0, 1, or 2;
• R21 is independently selected from halogen, —NO2, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, hydroxy(C1-C6 alkyl), hydroxy(C1-C6 alkoxy), alkoxy(C1-C6 alkyl), alkoxy(C1-C6 alkoxy), and amino(C1-C6 alkyl);
• or
• R22 is independently selected from halogen, —CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy;
• R23 is selected from halogen, —CO2H, —CO2(C1-C6 alkyl), —CO(C1-C6 alkyl), —CONH2, —CONH(C1-C6 alkyl), —CON(C1-C6 alkyl)2, —CONH—OH, —CONH—OCO(C1-C6 alkyl), —CONH—NH2, —CONH—S(O)2R25, —SO2OH, —SO2(C1-C6 alkyl), —SO2N(R25)2, —SO2NH—COCH3, —S(O)(NR25)R25, —NH—SO2R25, —NHCO—NHSO2R25, —PO(OH)2, —PO(OH)R25, pyrazolyl, and tetrazolyl, wherein
• each R25 is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 haloalkyl;
• R26 is —OH, C1-C6 alkoxy, —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;
• and
• X is CH2, CH, O, S, or NH, and Y is O, S, or NH, where X and Y, together with the atoms to which they are attached, form a 10- to 16-member macrocycle, the macrocycle optionally substituted with one or more R24, wherein
• each R24 is independently selected from the group consisting of halogen, —NO2, —CN, C1-C6alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, hydroxy(C1-C6 alkyl), hydroxy(C1-C6 alkoxy), alkoxy(C1-C6 alkyl), alkoxy(C1-C6 alkoxy), and amino(C1-C6 alkyl),
• or two R24 groups, together with the carbon to which they are attached, form a ═O.

A compound of the formula (I):

• or a pharmaceutically acceptable salt thereof, wherein
• ring A represents a phenyl or a naphthyl ring;
• ring B and ring C form a bicyclic heteroaryl, bicyclic heterocyclyl, or bicyclic cycloalkyl moiety, where ring B is a monocyclic heteroaryl, monocyclic heterocyclyl, or monocyclic cycloalkyl ring, and ring C is a phenyl or monocyclic 6-membered heteroaryl ring;
• m is an integer 0, 1, 2, or 3;
• n is an integer 0, 1, or 2;
• R1 is independently selected from halogen, —NO2, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, hydroxy(C1-C6 alkyl), hydroxy(C1-C6 alkoxy), alkoxy(C1-C6 alkyl), alkoxy(C1-C6 alkoxy), and amino(C1-C6 alkyl);
• or
• R2 is independently selected from halogen, —CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy;
• R3 is selected from halogen, —CO2H, —CO2(C1-C6 alkyl), —CO(C1-C6 alkyl), —CONH2, —CONH(C1-C6 alkyl), —CON(C1-C6 alkyl)2, —CONH—OH, —CONH—OCO(C1-C6 alkyl), —CONH—NH2, —CONH—S(O)2R5, —SO2OH, —SO2(C1-C6 alkyl), —SO2N(R5)2, —SO2NH—COCH3, —S(O)(NR5)R5, —NH—SO2R5, —NHCO—NHSO2R5, —PO(OH)2, —PO(OH)R5, pyrazolyl, and tetrazolyl, wherein
• each R5 is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl optionally substituted with C1-C4 alkyl, and phenyl, and monocyclic heteroaryl;
• and
• X is CH2, CH, O, S, or NH, and Y is O, S, or NH, where X and Y, together with the atoms to which they are attached, form a 10- to 16-member macrocycle, the macrocycle optionally substituted with one or more R4, wherein
• each R4 is independently selected from the group consisting of halogen, —NO2, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, hydroxy(C1-C6 alkyl), hydroxy(C1-C6 alkoxy), alkoxy(C1-C6 alkyl), alkoxy(C1-C6 alkoxy), and amino(C1-C6 alkyl),
• or two R4 groups, together with the carbon to which they are attached, form a ═O;

A compound of the formula (II) or (Ill):

• or a pharmaceutically acceptable salt thereof, wherein
• ring A1 represents a phenyl or a naphthyl ring;
• ring B1 and ring C1 form a bicyclic heteroaryl, bicyclic heterocyclyl, or bicyclic cycloalkyl moiety, where ring B1 is a monocyclic heteroaryl, monocyclic heterocyclyl, or monocyclic cycloalkyl ring, and ring C1 is a phenyl or monocyclic 6-membered heteroaryl ring;
• p is an integer 0, 1, or 2;
• q is an integer 0, 1, or 2;
• R11 is independently selected from halogen, —NO2, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, hydroxy(C1-C6 alkyl), hydroxy(C1-C6 alkoxy), alkoxy(C1-C6 alkyl), alkoxy(C1-C6 alkoxy), and amino(C1-C6 alkyl);
• or
• R12 is independently selected from halogen, —CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy;
• R13 is selected from halogen, —CO2H, —CO2(C1-C6 alkyl), —CO(C1-C6 alkyl), —CONH2, —CONH(C1-C6 alkyl), —CON(C1-C6 alkyl)2, —CONH—OH, —CONH—OCO(C1-C6 alkyl), —CONH—NH2, —CONH—S(O)2R15, —SO2OH, —SO2(C1-C6 alkyl), —SO2N(R15)2, —SO2NH—COCH3, —S(O)(NR15)R15, —NH—SO2R15, —NHCO—NHSO2R15, —PO(OH)2, —PO(OH)R15, pyrazolyl, and tetrazolyl, wherein each R15 is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl optionally substituted with C1-C4 alkyl, phenyl, and monocyclic heteroaryl;
• R16 is —OH, C1-C6 alkoxy, —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;
• and
• X is CH2, CH, O, S, or NH, and Y is O, S, or NH, where X and Y, together with the atoms to which they are attached, form a 10- to 16-member macrocycle, the macrocycle optionally substituted with one or more R14, wherein
• each R14 is independently selected from the group consisting of halogen, —NO2, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, hydroxy(C1-C6 alkyl), hydroxy(C1-C6 alkoxy), alkoxy(C1-C6 alkyl), alkoxy(C1-C6 alkoxy), and amino(C1-C6 alkyl),
• or two R14 groups, together with the carbon to which they are attached, form a═O.