Heteroaryl estrogen receptor modulators and uses thereof

A compound selected from Formulas I, II, and III:

• and
• stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein:
• A, B, C, and D are independently selected from CR6 and N;
• Y1 is CRb or N;
• Y2 is —(CH2)—, —(CH2CH2)—, or NRa;
• Y3 is NRa or C(Rb)2;
• where one of Y1, Y2 and Y3 is N or NRa;
• Ra is selected from H, C1-C6 alkyl, C2-C8 alkenyl, propargyl, C3-C6 cycloalkyl, and C3-C6 heterocyclyl, optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, OH, OCH3, and SO2CH3;
• Rb is independently selected from H, —O(C1-C3 alkyl), C1-C6 alkyl, C2-C8 alkenyl, propargyl, —(C1-C6 alkyldiyl)-(C3-C6 cycloalkyl), C3-C6 cycloalkyl, and C3-C6 heterocyclyl, optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, —CH2F, —CHF2, —CF3, —CH2CF3, —CH2CHF2, —CH2CH2F, OH, OCH3, and SO2CH3,
• Rc is selected from H, C1-C6 alkyl, allyl, propargyl, optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, OH, OCH3, and SO2CH3;
• Cy is selected from C6-C20 aryldiyl, C3-C12 carbocyclyldiyl, C2-C20 heterocyclyldiyl, and C1-C20 heteroaryldiyl;
• Z1 is selected from CRa and N;
• Z2 is selected from O, S, and NRa
• Z3 is selected from O, S, NRa C1-C6 alkyldiyl, C1-C6 fluoroalkyldiyl, O—(C1-C6 alkyldiyl), O—(C1-C6 fluoroalkyldiyl), C(O), and a bond;
• R1, R2, R3, R4, R8, and R9 are independently selected from H, F, Cl, Br, I, —CN, —CH3, —CH2CH3, —CH(CH3)2, —CH2CH(CH3)2, —CH2OH, —CH2OCH3, —CH2CH2OH, —C(CH3)2OH, —CH(OH)CH(CH3)2, —C(CH3)2CH2OH, —CH2CH2SO2CH3, —CH2OP(O)(OH)2, —CH2F, —CHF2, —CH2NH2, —CH2NHSO2CH3, —CH2NHCH3, —CH2N(CH3)2, —CF3, —CH2CF3, CH2CHF2, —CH(CH3)CN, —C(CH3)2CN, —CH2CN, —CO2H, —COCH3, —CO2CH3, —CO2C(CH3)3, —COCH(OH)CH3, —CONH2, —CONHCH3, —CONHCH2CH3, —CONHCH(CH3)2, —CON(CH3)2, —C(CH3)2CONH2, —NH2, —NHCH3, —N(CH3)2, NHCOCH3, —N(CH3)COCH3, —NHS(O)2CH3, —N(CH3)C(CH3)2CONH2, N(CH3)CH2CH2S(O)2CH3, —NO2, ═O, —OH, —OCH3, —OCH2CH3, —OCH2CH2OCH3, —OCH2CH2OH, —OCH2CH2N(CH3)2, —OP(O)(OH)2, —S(O)2N(CH3)2, —SCH3, —S(O)2CH3, —S(O)3H, cyclopropyl, cyclopropylamide, cyclobutyl, oxetanyl, azetidinyl, 1-methylazetidin-3-yl)oxy, N-methyl-N-oxetan-3-ylamino, azetidin-1-ylmethyl, benzyloxyphenyl, pyrrolidin-1-yl, pyrrolidin-1-yl-methanone, piperazin-1-yl, morpholinomethyl, morpholino-methanone, and morpholino;
• or R3 and R8 form a 4, 5, 6, or 7-membered carbocylic or heterocyclic ring;
• R5 is selected from H, C1-C9 alkyl, C3-C9 cycloalkyl, C3-C9 heterocycle, C6-C9 aryl, C6-C9 heteroaryl, —(C1-C6 alkyldiyl)-(C3-C9 cycloalkyl), —(C1-C6 alkyldiyl)-(C3-C9 heterocycle), C(O)Rb, C(O)NRa, SO2Ra, and SO2NRa, optionally substituted with one or more of halogen, CN, ORa, N(Ra)2, C1-C9 alkyl, C3-C9 cycloalkyl, C3-C9 heterocycle, C6-C9 aryl, C6-C9 heteroaryl, C(O)Rb, C(O)NRa, SO2Ra, and SO2NRa;
• or R3 and R5 form a 4, 5, 6, or 7-membered heterocyclic ring;
• or Cy and R5 form a 4, 5, 6, or 7-membered heterocyclic ring;
• R6 is selected from H, F, Cl, Br, I, —CN, —CH3, —CH2CH3, —CH(CH3)2, —CH2CH(CH3)2, —CH2OH, —CH2OCH3, —CH2CH2OH, —C(CH3)2OH, —CH(OH)CH(CH3)2, —C(CH3)2CH2OH, —CH2CH2SO2CH3, —CH2OP(O)(OH)2, —CH2F, —CHF2, —CH2NH2, —CH2NHSO2CH3, —CH2NHCH3, —CH2N(CH3)2, —CF3, —CH2CF3, —CH2CHF2, —CH2CH2F, —CH(CH3)CN, —C(CH3)2CN, —CH2CN, —CO2H, —COCH3, —CO2CH3, —CO2C(CH3)3, —COCH(OH)CH3, —CONH2, —CONHCH3, —CONHCH2CH3, —CONHCH(CH3)2, —CON(CH3)2, —C(CH3)2CONH2, —NH2, —NHCH3, —N(CH3)2, —NHCOCH3, —N(CH3)COCH3, —NHS(O)2CH3, —N(CH3)C(CH3)2CONH2, —N(CH3)CH2CH2S(O)2CH3, —NO2, ═O, —OH, —OCH3, —OCH2CH3, —OCH2CH2OCH3, —OCH2CH2OH, —OCH2CH2N(CH3)2, —OP(O)(OH)2, —S(O)2N(CH3)2, —SCH3, —S(O)2CH3, —S(O)3H, cyclopropyl, cyclopropylamide, cyclobutyl, oxetanyl, azetidinyl, 1-methylazetidin-3-yl)oxy, N-methyl-N-oxetan-3-ylamino, azetidin-1-ylmethyl, benzyloxyphenyl, pyrrolidin-1-yl, pyrrolidin-1-yl-methanone, piperazin-1-yl, morpholinomethyl, morpholino-methanone, and morpholino;
• R7 is selected from H, C1-C6 alkyl, C2-C8 alkenyl, and propargyl;
• or R7 and Cy form a spiro, 4, 5, 6, or 7-membered carbocyclic or heterocyclic ring;
• and
• n is selected from 1 and 2;
• where alkyldiyl, fluoroalkyldiyl, aryldiyl, carbocyclyldiyl, heterocyclyldiyl, and heteroaryldiyl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, —CN, —CH3, —CH2CH3, —CH(CH3)2, —CH2CH(CH3)2, —CH2OH, —CH2OCH3, —CH2CH2OH, —C(CH3)2OH, —CH(OH)CH(CH3)2, —C(CH3)2CH2OH, —CH2CH2SO2CH3, —CH2OP(O)(OH)2, —CH2F, —CHF2, —CF3, —CH2CF3, —CH2CHF2, CH2CH2F, —CH(CH3)CN, —C(CH3)2CN, —CH2CN, —CH2NH2, —CH2NHSO2CH3, —CH2NHCH3, —CH2N(CH3)2, —CO2H, —COCH3, —CO2CH3, —CO2C(CH3)3, —COCH(OH)CH3, —CONH2, —CONHCH3, —CON(CH3)2, —C(CH3)2CONH2, —NH2, —NHCH3, —N(CH3)2, NHCOCH3, —N(CH3)COCH3, —NHS(O)2CH3, —N(CH3)C(CH3)2CONH2, N(CH3)CH2CH2S(O)2CH3, —NO2, ═O, —OH, —OCH3, —OCH2CH3, —OCH2CH2OCH3, —OCH2CH2OH, —OCH2CH2N(CH3)2, —OP(O)(OH)2, —S(O)2N(CH3)2, —SCH3, —S(O)2CH3, —S(O)3H, cyclopropyl, cyclopropylamide, cyclobutyl, oxetanyl, azetidinyl, 1-methylazetidin-3-yl)oxy, N-methyl-N-oxetan-3-ylamino, azetidin-1-ylmethyl, benzyloxyphenyl, pyrrolidin-1-yl, pyrrolidin-1-yl-methanone, piperazin-1-yl, morpholinomethyl, morpholino-methanone, and morpholino;
• with the proviso that for a Formula I compound when n is 1;
• A, B, C, and D are each CR6;
• and Z2 is N;
• then R7 is not H.