Acyclic amide and sulfonamide ligands for the estrogen receptor

A compound of structural formula (I)

• 81
• the pharmaceutically acceptable salts, stereoisomers, and prodrugs thereof, and the pharmaceutically acceptable salts of said steroisomers and prodrugs, wherein:
• Q is
• 82
• or a six-membered heteroaryl ring containing one or two nitrogen atoms, wherein said heteroaryl ring is optionally substituted with R9 and/or Z;
• R1, R2, R3, and R9 are, independently, hydrogen;
• hydroxy;
• halogen;
• cyano;
• —(C1-C6)alkyl, optionally substituted with 1-3 fluorine atoms;
• and —O(C1-C6)alkyl, optionally substituted with 1-3 fluorine atoms;
• R4 is hydrogen or —(C1-C6)alkyl;
• R5 is —(C1-C7)alkyl, optionally substituted with from 1-6 halogen atoms;
• —(C2-C6)alkenyl;
• —(C2-C6)alkenyl-M;
• or —(CH2)n—M, wherein n is 0-5;
• and wherein M is:
• (i) a fully saturated 3-8 membered ring, or a partially saturated, or fully saturated 5-8 membered ring, optionally having from 1-4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur;
• or
• (ii) a bicyclic ring comprising two fused partially saturated, fully saturated, or fully unsaturated 5- or 6-membered rings, optionally having from 14 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur;
• wherein
• M is optionally substituted with from 1-3 substituents independently selected from the group consisting of hydroxy;
• halogen;
• cyano;
• nitro;
• formyl;
• amino;
• carbamoyl;
• thiol;
• —(C1-C6)alkyl or —O(C1-C6)alkyl, optionally substituted with from 1-5 halogen atoms;
• —(C3-C8)cycloalkyl or phenyl, optionally substituted with from 1-3 halogen atoms;
• —SO(C1-C6)alkyl or—SO2(C1-C6)alkyl, optionally substituted with from 1-5 halogen atoms;
• —S(C1-C6)alkyl, optionally substituted with from 1-5 halogen atoms;
• —(C1-C4)alkoxycarbonyl;
• —(C1-C6)alkyl-(C3-C8)cycloalkyl;
• —(CO—C4)sulfonamido;
• mono-N- or di-N,N—(C1-C4)alkylcarbamoyl;
• mono-N or di-N,N—(C1-C4)alkylamino-SO2;
• mono-N or di-N,N—(C1-C4)alkylamino;
• —(C1-C8)alkanoyl;
• —(C1-C4)alkanoylamino;
• or —(C1-C4)alkoxycarbonylamino;
• X is CO or SO2;
• Z is —O(CH2)n—NRaRb;
• —(CH2)n—NRaRb;
• —CH═CH—C(O)—NRaRb;
• —(CH2)n—COOH;
• —CH=CH—COOH;
• —O(C1-C6)alkyl;
• —CH═CH—C(O)O(C1-C6)alkyl;
• and —(CH2)n—OH;
• wherein each n is 0-5 inclusive, provided that when Z is —O—(CH2)n—NRaRb, n is 2-5;
• Ra and Rb are, independently, hydrogen;
• —(C1-C6)alkyl;
• —(CH2)n—(C3-C8)cycloalkyl;
• —(CH2)2-5—OH;
• —(CH2)n-phenyl;
• —(CH2)n-heteroaryl;
• —(CH2)n-heterocycloalkyl;
• and
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• wherein each n is 0-5 inclusive, and wherein said cycloalkyl, phenyl, heteroaryl, and heterocycloalkyl is optionally substituted with from 1-3 substituents independently selected from the group consisting of hydroxy;
• halogen;
• cyano;
• nitro;
• amino;
• carbamoyl;
• —(C1-C6)alkyl or —O(C1-C6)alkyl, optionally substituted with from 1-5 halogen atoms;
• —(C1-C3)alkyl-O(C1-C3)alkyl;
• —(C1-C4)OH;
• carboxylate;
• —(C1-C3)phenyl;
• —(C3-C8)cycloalkyl;
• phenyl, optionally substituted with from 1-3 halogen atoms;
• —SO(C1-C6)alkyl or —SO2(C1-C6)alkyl, optionally substituted with from 1-5 halogen atoms;
• —S(C1-C6)alkyl, optionally substituted with from 1-5 halogen atoms;
• —(C1-C4)alkoxycarbonyl;
• —(C1-C6)alkyl-(C3-C8)cycloalkyl;
• sulfonamido;
• —(C1-C4)alkylsulfonamido;
• mono-N- or di-N,N—(C1-C4)alkylcarbamoyl;
• mono-N or di-N,N-(C1-C4)alkylamino-SO2;
• mono-N or di-N,N—(C1-C4)alkylamino;
• —(C1-C8)alkanoyl;
• —(C1-C4)alkanoylamino;
• or —(C1-C4)alkoxycarbonylamino;
• or
• Ra and Rb, taken together with the nitrogen atom to which they are attached, form a 3-7 membered heterocycloalkyl ring having from 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• or a 5-7 membered ring fused to a phenyl ring, wherein said 3-7 membered heterocycloalkyl ring, or said 5-7 membered ring fused to a phenyl ring, is optionally substituted with from 1-3 substituents independently selected from the group consisting of hydroxy;
• halogen;
• cyano;
• nitro;
• amino;
• carbamoyl;
• —(C1-C6)alkyl or —O(C1-C6)alkyl, optionally substituted with from 1-5 halogen atoms;
• —(C1-C3)alkyl-O(C1-C3)alkyl;
• —(C1-C4)OH;
• carboxylate;
• —(C1-C3)phenyl;
• —(C3-C8)cycloalkyl;
• phenyl, optionally substituted with from 1-3 halogen atoms;
• —SO(C1-C6)alkyl or —SO2(C1-C6)alkyl, optionally substituted with from 1-5 halogen atoms;
• —S(C1-C6)alkyl, optionally substituted with from 1-5 halogen atoms;
• —(C1-C4)alkoxycarbonyl;
• —(C1-C6)alkyl-(C3-C8)cycloalkyl;
• —(C0-C4)sulfonamido;
• —(C1-C4)cycloalkylsulfonamido;
• mono-N- or di-N,N—(C1-C4)alkylcarbamoyl;
• mono-N or di-N,N—(C1-C4)alkylamino-SO2;
• mono-N or di-N,N—(C1-C4)alkylamino;
• —(C1-C8)alkanoyl;
• —(C1-C4)alkanoylamino;
• or —(C1-C4)alkoxycarbonylamino.