Estrogen receptor modulators and uses thereof

A compound of Formula (XI), or a pharmaceutically acceptable salt, or N-oxide thereof:

• wherein,
• ring B is phenyl, naphthyl, 5-membered monocyclic heteroaryl, 6-membered monocyclic heteroaryl, or 8-, 9- or 10-membered bicyclic heteroaryl;
• ring C is phenyl, 5-membered monocyclic heteroaryl or 6-membered monocyclic heteroaryl;
• R1 is —C(═O)—Z, or a carboxylic acid bioisostere;
• Z is —OH, —OR9, —NR7R8, —NR7S(═O)2R9, —NHOH or —NR7OR9;
• R3 is H, halogen, —CN, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6fluoroalkyl, or C1-C6heteroalkyl;
• each Ra is independently selected from H, halogen, —NR7R8, —CN, —OH, —OR9, —SR8, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C2-C6alkenyl, C2-C6alkynyl, substituted or unsubstituted C1-C6fluoroalkyl, and substituted or unsubstituted C1-C6heteroalkyl;
• each Rb is independently selected from H, halogen, —NR7R8, —CN, —OH, —OR9, —SR8, —S(═O)R9, —S(═O)2R9, —NHS(═O)2R9, —S(═O)2N(R8)2, —C(═O)R9, —OC(═O)R9, —CO2R8, —OCO2R9, —C(═O)N(R8)2, —OC(═O)N(R8)2, —NR7C(═O)N(R8)2, —NR7C(═O)R9, —NR7C(═O)OR9, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C2-C6alkenyl, substituted or unsubstituted C2-C6alkynyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C1-C6-fluoroalkoxy, substituted or unsubstituted C1-C6alkoxy, substituted or unsubstituted phenyl and substituted or unsubstituted monocyclic heteroaryl;
• each Rc is independently selected from H, halogen, —CN, —OH, —OR9, C1-C6alkyl, or C1-C6fluoroalkyl;
• R4 is H, F, Cl, —CN, —OH, —OR9, —SR8, —S(═O)R9, —S(═O)2R9, —NHS(═O)2R9, —S(═O)2N(R8)2, —C(═O)R9, —OC(═O)R9, —CO2R8, —C(═O)N(R8)2, —OC(═O)N(R8)2, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6fluoroalkyl, or C1-C6heteroalkyl;
• R5 is H, C1-C4alkyl, or halogen;
• R6 is H, C1-C4alkyl, or halogen;
• R7 is H, or C1-C6alkyl;
• each R8 is independently selected from H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C2-C6alkenyl, substituted or unsubstituted C2-C6alkynyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C10cycloalkyl, substituted or unsubstituted C2-C10heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted benzyl;
• each R9 is independently selected from substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C3-C10cycloalkyl, substituted or unsubstituted C2-C10heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted benzyl;
• m is 0, 1, 2, or 3;
• n is 0, 1, 2, or 3;
• p is 0, 1, or 2;
• and
• r is 1, 2, 3, or 4;
• provided that the compound is not
• (E)-3-(4-((E)-1-(Benzo[d]thiazol-5-yl)-2-(2-chloro-4-fluorophenyl)-2-cyclobutylvinyl)phenyl)acrylic acid;
• (E)-3-(4-((E)-1-(Benzo[d]thiazol-5-yl)-2-cyclobutyl-2-(4-methylthiophen-3-yl)vinyl)phenyl)acrylic acid;
• (E)-3-(4-((E)-1-(Benzo[d]thiazol-5-yl)-2-cyclobutyl-2-phenylvinyl)phenyl)acrylic acid;
• or
• 5-((E)-1-(4-((E)-2-(2H-Tetrazol-5-yl)vinyl)phenyl)-2-cyclobutyl-2-(4-methylthiophen-3-yl)vinyl)benzo[d]thiazole.

A compound of Formula (VI), or a pharmaceutically acceptable salt, or N-oxide thereof:

• wherein,
• ring B is phenyl, naphthyl, 5-membered monocyclic heteroaryl, 6-membered monocyclic heteroaryl, or 8-, 9- or 10-membered bicyclic heteroaryl;
• ring C is phenyl, 5-membered monocyclic heteroaryl or a 6-membered monocyclic heteroaryl;
• R1 is —C(═O)—Z, or a carboxylic acid bioisostere;
• Z is —OH, —OR9, —NR7R8, —NR7S(═O)2R9, —NHOH or —NR7OR9;
• each Ra is independently selected from H, halogen, —NR7R8, —CN, —OH, —OR9, —SR8, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C2-C6alkenyl, C2-C6alkynyl, substituted or unsubstituted C1-C6fluoroalkyl, and substituted or unsubstituted C1-C6heteroalkyl;
• each Rb is independently selected from H, halogen, —NR7R8, —CN, —OH, —OR9, —SR8, —S(═O)R9, —S(═O)2R9, —NHS(═O)2R9, —S(═O)2N(R8)2, —C(═O)R9, —OC(═O)R9, —CO2R8, —OCO2R9, —C(═O)N(R8)2, —OC(═O)N(R8)2, —NR7C(═O)N(R8)2, —NR7C(═O)R9, —NR7C(═O)OR9, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C2-C6alkenyl, substituted or unsubstituted C2-C6alkynyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C1-C6-fluoroalkoxy, substituted or unsubstituted C1-C6alkoxy, substituted or unsubstituted phenyl and substituted or unsubstituted monocyclic heteroaryl;
• each Rc is independently selected from H, halogen, —CN, —OH, —OR9, C1-C6alkyl, or C1-C6fluoroalkyl;
• R3 is H, halogen, —CN, C1-C6alkyl, C1-C6fluoroalkyl, or C1-C6heteroalkyl;
• R4 is H, halogen, —CN, —OH, —OR9, —SR8, —S(═O)R9, —S(═O)2R9, —NHS(═O)2R9, —S(═O)2N(R8)2, —C(═O)R9, —OC(═O)R9, —CO2R8, —C(═O)N(R8)2, —OC(═O)N(R8)2, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6fluoroalkyl, or C1-C6heteroalkyl;
• R5 is H, C1-C4alkyl, or halogen;
• R6 is H, C1-C4alkyl, or halogen;
• R7 is H, or C1-C6alkyl;
• each R8 is independently selected from H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C2-C6alkenyl, substituted or unsubstituted C2-C6alkynyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C10cycloalkyl, substituted or unsubstituted C2-C10heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted benzyl;
• each R9 is independently selected from substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C3-C10cycloalkyl, substituted or unsubstituted C2-C10heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted benzyl;
• m is 0, 1, 2, or 3;
• n is 0, 1, 2, or 3;
• p is 0, 1, or 2;
• and
• r is 1, 2, 3, or 4;
• provided that the compound is not (E)-3-(4-((E)-2-(2-Chloro-4-fluorophenyl)-2-cyclobutyl-1-(imidazo[1,2-a]pyridin-6-yl)vinyl)phenyl)acrylic acid.