Farnesoid x receptor agonists and uses thereof

A compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof:

• wherein:
• ring A is a 5-membered heteroaryl that is oxazolyl, thiazolyl, pyrazolyl, furanyl, thienyl, pyrrolyl, imidazolyl, triazolyl, tetrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, or thiadiazolyl;
• or ring A is a 6-membered heteroaryl that is pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, or triazinyl;
• X1, X5, X6, and X7 are each independently C(H), C(R7), or N, wherein at least one of X1, X5, X6, and X7 is C(H);
• R1 is selected from H, halogen, —CN, —OH, —N(R17)2, —NR17S(═O)2(C1-C4alkyl), —S(═O)2N(R17)2, —OC(═O)(C1-C4alkyl), —CO2H, —CO2(C1-C4alkyl), —C(═O)N(R17)2, —NR17C(═O)(C-C4alkyl), —NR17C(═O)O(C1-C4alkyl), —OC(═O)N(R17)2, —NR17C(═O)N(R17)2, —SH, —S(C1-C4alkyl), —S(═O)(C1-C4alkyl), —S(═O)2(C1-C4alkyl), C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, C1-C4heteroalkyl, and monocyclic C2-C5heterocycloalkyl;
• X2 is CR2 or N;
• R2 is H, halogen, —CN, —OH, —N(R17)2, —NR17S(═O)2(C1-C4alkyl), —S(═O)2N(R17)2, —OC(═O)(C1-C4alkyl), —CO2H, —CO2(C1-C4alkyl), —C(═O)N(R17)2, —NR17C(═O)(C1-C4alkyl), —NR17C(═O)O(C1-C4alkyl), —OC(═O)N(R17)2, —NR17C(═O)N(R17)2, —SH, —S(C1-C4alkyl), —S(═O)(C1-C4alkyl), —S(═O)2(C1-C4alkyl), C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, C1-C4heteroalkyl, or monocyclic C2-C5heterocycloalkyl;
• or R1 and R2 are taken together with the intervening atoms to form a fused 5- or 6-membered ring with 0-3 N atoms and 0-2 O or S atoms in the ring, wherein the fused 5- or 6-membered ring is optionally substituted with halogen or C1-C4alkyl;
• X3 is CR3 or N;
• R3 is H, halogen, —CN, —OH, —N(R17)2, —NR17S(═O)2(C1-C4alkyl), —OC(═O)(C1-C4alkyl), —CO2H, —CO2(C1-C4alkyl), —C(═O)N(R17)2, —NR17C(═O)(C1-C4alkyl), C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, or C1-C4heteroalkyl;
• each X4 is independently CH or N;
• R4 is H, F, or —CH3;
• R5 is H, F, or —CH3;
• each R6 is independently H, F, —OH, or —CH3;
• L is absent, —Y2-L1-, -L1-Y2—, cyclopropylene, cyclobutylene, or bicyclo[1.1.1]pentylene;
• Y2 is absent, —O—, —S—, —S(═O)—, —S(═O)2—, —S(═O)2NR17—, —CH2—, —CH═CH—, —C≡C—, —C(═O)—, —C(═O)O—, —OC(═O)—, —OC(═O)O—, —C(═O)NR17—, —NR17C(═O)—, —OC(═O)NR17—, —NR17C(═O)O—, —NR17C(═O)NR17—, —NR17S(═O)2-, or —NR17—;
• L1 is absent or C1-C4alkylene;
• each R7 is independently selected from halogen, —CN, —OH, C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, and C1-C4heteroalkyl;
• R8 is C4-C5alkyl or C1-C8haloalkyl;
• R9 is H, F or —CH3;
• L2 is absent or —C1-C6alkylene-
• R11 is H, F, or —CH3;
• R12 is H or C1-C6alkyl;
• each R17 is independently H or C1-C6alkyl;
• each R18 is independently halogen, —CN, —OH, —N(R17)2, —NR17S(═O)2(C1-C4alkyl), —S(C1-C4alkyl), —S(═O)(C1-C4alkyl), —S(═O)2(C1-C4alkyl), —S(═O)2N(R17)2, —C(═O)(C1-C4alkyl), —OC(═O)(C1-C4alkyl), —CO2H, —CO2(C1-C4alkyl), —NR17C(═O)(C1-C4alkyl), —C(═O)N(R17)2, —NR17C(═O)O(C1-C4alkyl), —OC(═O)N(R17)2, C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, C1-C4heteroalkyl, C3-C6cycloalkyl, monocyclic C2-C6heterocycloalkyl, phenyl, or monocyclic heteroaryl;
• m is 0, 1, or 2;
• and
• n is 0, 1, or 2.

A compound of Formula (III), or a pharmaceutically acceptable salt or solvate thereof:

• wherein:
• ring A is a 5-membered heteroaryl that is furanyl, thienyl, pyrrolyl, imidazolyl, triazolyl, tetrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, or thiadiazolyl;
• or ring A is a 6-membered heteroaryl that is pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, or triazinyl;
• X1, X5, X6, and X7 are each independently C(R7) or N, wherein at least one of X1, X5, X6, and X7 is C(R7);
• R1 is selected from H, halogen, —CN, —OH, —N(R17)2, —NR17S(═O)2(C1-C4alkyl), —S(═O)2N(R17)2, —OC(═O)(C1-C4alkyl), —CO2H, —CO2(C1-C4alkyl), —C(═O)N(R17)2, —NR17C(═O)(C1-C4alkyl), —NR17C(═O)O(C1-C4alkyl), —OC(═O)N(R17)2, —NR17C(═O)N(R17)2, —SH, —S(C1-C4alkyl), —S(═O)(C1-C4alkyl), —S(═O)2(C1-C4alkyl), C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, C1-C4heteroalkyl, C3-C6cycloalkyl, and monocyclic C2-C5heterocycloalkyl;
• X2 is CR2 or N;
• R2 is H, halogen, —CN, —OH, —N(R17)2, —NR17S(═O)2(C1-C4alkyl), —S(═O)2N(R17)2, —OC(═O)(C1-C4alkyl), —CO2H, —CO2(C1-C4alkyl), —C(═O)N(R17)2, —NR17C(═O)(C1-C4alkyl), —NR17C(═O)O(C1-C4alkyl), —OC(═O)N(R17)2, —NR17C(═O)N(R17)2, —SH, —S(C1-C4alkyl), —S(═O)(C1-C4alkyl), —S(═O)2(C1-C4alkyl), C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, C1-C4heteroalkyl, C3-C6cycloalkyl, or monocyclic C2-C5heterocycloalkyl;
• or R1 and R2 are taken together with the intervening atoms to form a fused 5- or 6-membered ring with 0-3 N atoms and 0-2 O or S atoms in the ring, wherein the fused 5- or 6-membered ring is optionally substituted with halogen or C1-C4alkyl;
• X3 is CR3 or N;
• R3 is H, halogen, —CN, —OH, —N(R17)2, —NR17S(═O)2(C1-C4alkyl), —OC(═O)(C1-C4alkyl), —CO2H, —CO2(C1-C4alkyl), —C(═O)N(R17)2, —NR17C(═O)(C1-C4alkyl), C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, or C1-C4heteroalkyl;
• each X4 is independently CH, CF, or N;
• each R6 is independently H, F, —OH, or —CH3;
• L is absent, —Y2-L1 -, -L1-Y2—, cyclopropylene, cyclobutylene, or bicyclo[1.1.1]pentylene;
• Y2 is absent, —O—, —S—, —S(═O)—, —S(═O)2—, —S(═O)2NR17—, —CH2—, —CH═CH—, —C≡C—, —C(═O)—, —C(═O)O—, —OC(═O)—, —OC(═O)O—, —C(═O)NR17—, —NR17C(═O)—, —OC(═O)NR17—, —NR17C(═O)O—, —NR17C(═O)NR17—, —NR17S(═O)2-, or —NR17—;
• L1 is absent or C1-C4alkylene;
• each R7 is independently selected from H, halogen, —CN, —OH, C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, C3-C6cycloalkyl, and C1-C4heteroalkyl;
• R8 is H, C1-C8alkyl, C1-C4alkoxy, C1-C8fluoroalkyl, C1-C8heteroalkyl, —C(═O)(C1-C4alkyl), —CO2(C1-C4alkyl), —N(R17)2, —C(═O)N(R17)2, —S(═O)2(C1-C4alkyl), —S(═O)2N(R17)2, C3-C6cycloalkyl, monocyclic C2-C6heterocycloalkyl, phenyl, or monocyclic heteroaryl, wherein C3-C6cycloalkyl, monocyclic C2-C6heterocycloalkyl, phenyl, or monocyclic heteroaryl are optionally substituted with 1, 2, or 3 groups selected from halogen and C1-C6alkyl;
• R9 is H, F, or —CH3;
• L2 is absent or C1-C6alkylene;
• R11 is H, F, or —CH3;
• R12 is H or C1-C6alkyl;
• each R17 is independently H or C1-C6alkyl;
• each R18 is independently halogen, —CN, —OH, —N(R17)2, —NR17S(═O)2(C1-C4alkyl), —S(C1-C4alkyl), —S(═O)(C1-C4alkyl), —S(═O)2(C1-C4alkyl), —S(═O)2N(R17)2, —C(═O)(C1-C4alkyl), —OC(═O)(C1-C4alkyl), —CO2H, —CO2(C1-C4alkyl), —NR17C(═O)(C1-C4alkyl), —C(═O)N(R17)2, —NR17C(═O)O(C1-C4alkyl), —OC(═O)N(R17)2, C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, C1-C4heteroalkyl, monocyclic C2-C6heterocycloalkyl, phenyl, or monocyclic heteroaryl;
• m is 0, 1, or 2;
• n is 0, 1, or 2;
• and
• t is 0, 1, or 2.