Farnesoid X receptor agonists and uses thereof

A compound that has the structure of Formula (I), 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;
• or ring A is phenyl;
• X1 is CH or N;
• R1 is H, D, halogen, —CN, —OH, —N(R15)2, —NR15S(═O)2(C1-C4alkyl), —S(═O)2N(R15)2, —OC(═O)(C1-C4alkyl), —CO2H, —CO2(C1-C4alkyl), —C(═O)N(R15)2, —NR15C(═O)(C1-C4alkyl), —NR 15C(═O)O(C1-C4alkyl), —OC(═O)N(R15)2, —NR15C(═O)N(R15)2, —SH, —S(C1-C4alkyl), —S(═O)(C1-C4alkyl), —S(═O)2(C1-C4alkyl), C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4deuteroalkyl, C1-C4deuteroalkoxy, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, C1-C4heteroalkyl, or substituted or unsubstituted monocyclic C2-C5heterocycloalkyl;
• X2 is CR2 or N;
• R2 is H, D, halogen, —CN, —OH, —N(R15)2, —NR15S(═O)2(C1-C4alkyl), —S(═O)2N(R15)2, —OC(═O)(C1-C4alkyl), —CO2H, —CO2(C1-C4alkyl), —C(═O)N(R15)2, —NR15C(═O)(C1-C4alkyl), —NR15C(═O)O(C1-C4alkyl), —OC(═O)N(R15)2, —NR15C(═O)N(R15)2, —SH, —S(C1-C4alkyl), —S(═O)(C1-C4alkyl), —S(═O)2(C1-C4alkyl), C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4deuteroalkyl, C1-C4deuteroalkoxy, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, C1-C4heteroalkyl, or substituted or unsubstituted monocyclic C2-C5heterocycloalkyl;
• or R1 and R2 are taken together with the intervening atoms to form a substituted or unsubstituted fused 5- or 6-membered ring with 0-3 N atoms and 0-2 O or S atoms in the ring;
• X3 is CR3 or N;
• R3 is H, D, halogen, —CN, —OH, —N(R15)2, —NR15S(═O)2(C1-C4alkyl), —OC(═O)(C1-C4alkyl), —CO2H, —CO2(C1-C4alkyl), —C(═O)N(R15)2, —NR15C(═O)(C1-C4alkyl), C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4deuteroalkyl, C1-C4deuteroalkoxy, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, or C1-C4heteroalkyl;
• each X4 is independently CH or N;
• R4 and R5 are taken together to form a bridge that is —CH2— or —CH2CH2—;
• each R6 is independently H, D, F, —OH, or —CH3;
• m is 0, 1, or 2;
• R7 is H, D, halogen, —CN, —OH, C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4deuteroalkyl, C1-C4deuteroalkoxy, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, or C1-C4heteroalkyl;
• 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)2NR15—, —CH2—, —CH═CH—, —C≡C—, —C(═O)—, —C(═O)O—, —OC(═O)—, —OC(═O)O—, —C(═O)NR15—, —NR15C(═O)—, —OC(═O)NR15—, —NR15C(═O)O—, —NR15C(═O)NR15—, —NR15S(═O)2—, or —NR15;
• L1 is absent or substituted or unsubstituted C1-C4alkylene;
• R8 is H, D, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C1-C6heteroalkyl, —C(═O)(C1-C4alkyl), —CO2(C1-C4alkyl), —C(═O)N(R15)2, —S(═O)2(C1-C4alkyl), —S(═O)2N(R15)2, substituted or unsubstituted C3-C6cycloalkyl, or substituted or unsubstituted monocyclic C2-C6heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl;
• R9 is H, D, F or —CH3;
• R10 is C1-C6heteroalkyl, —C(═O)R14, —OC(═O)OR14, tetrazolyl, imidazole, 5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl, —S(═O)2N(R12)2, —NR15S(═O)2R14, —C(═O)NR15S(═O)2R14, —S(═O)2NR1C(═O)R14, —CH2N(R12)2, —C(═O)N(R12)2, —NR15C(═O)N(R12)2, —C(═NH)NH2, —NHC(═NH)NH2, —C(═O)NHC(═NH)NH2, —S(═O)2OH or —OP(═O)(OR15)2;
• or R10 is -L2-L3-L4-R13;
• L2 is absent, substituted or unsubstituted C1-C6alkylene, or substituted or unsubstituted C1-C6heteroalkylene;
• L3 is absent, —O—, —S—, —S(═O)—, —S(═O)2—, —NR15—, —C(═O)—, —C(═O)NR15—, —NR15C(═O)—, —C(═O)O—, —OC(═O)—, —OC(═O)NR15—, —NR15C(═O)NR15—, —NR15C(═O)O—, —OP(═O)(OR15)O—, or —(OCH2CH2)r—, r is 1 or 2;
• L4 is substituted or unsubstituted C1-C6alkylene, or substituted or unsubstituted C1-C6heteroalkylene;
• R13 is H, —CN, —N(R12)2, —NR15S(═O)2R14, —S(═O)2N(R12)2, —SR12, —S(═O)R14, —S(═O)2R14, —SO3H, —OP(═O)(OR15)2, —C(═O)R14, —OC(═O)OR14, —C(═O)N(R12)2, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6alkoxy, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C2-C6heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl;
• R11 is H, D, F, or —CH3;
• or R9 and R11 are taken together to form a bridge that is —CH2— or —CH2CH2—;
• each R12 is independently H, C1-C4alkyl, C1-C4deuteroalkyl, C1-C4fluoroalkyl, C1-C4heteroalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C2-C6heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, or substituted or unsubstituted monocyclic heteroaryl;
• R14 is C1-C4alkyl, C1-C4deuteroalkyl, C1-C4fluoroalkyl, C1-C4heteroalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C2-C6heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, or substituted or unsubstituted monocyclic heteroaryl;
• R15 is H or substituted or unsubstituted C1-C6alkyl;
• each R16 is independently H, D, halogen, —CN, —OH, —N(R15)2, —NR15S(═O)2(C1-C4alkyl), —S(C1-C4alkyl), —S(═O)(C1-C4alkyl), —S(═O)2(C1-C4alkyl), —S(═O)2N(R15)2, —C(═O)(C1-C4alkyl), —OC(═O)(C1-C4alkyl), —CO2H, —CO2(C1-C4alkyl), —NR15C(═O)(C1-C4alkyl), —C(═O)N(R15)2, —NR15C(═O)O(C1-C4alkyl), —OC(═O)N(R15)2, C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4deuteroalkyl, C1-C4deuteroalkoxy, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, C1-C4heteroalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted monocyclic C2-C6heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl;
• n is 0, 1, or 2.