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US 2004/0002524 A1Published application
Benzimidazole compounds and their use as estrogen agonists/antagonists
OwnerRichard Chesworth, Laura D. Gegnasinventors
Life of this patent
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Abstract
This invention relates to compounds, in particular benzimidazoles, that are useful as estrogen agonists and/or antagonists and pharmaceutical uses thereof. The present invention also relates to benzimidazoles that are selective for the ERβ receptor and pharmaceutical uses thereof.
Claims21
A compound of formula (I)
- 10
- or the pharmaceutically acceptable salts thereof;
- wherein:
- R1 and R2 are each independently selected from the group consisting of (C1-C6)alkyl;
- phenyl;
- (C2-C6)heteroaryl;
- (C3-C8)cycloalkyl, and (C4-C8)cycloalkenyl;
- wherein the (C1-C6)alkyl;
- phenyl;
- (C2-C6)heteroaryl;
- (C3-C8)cycloalkyl;
- or (C4-C8)cycloalkenyl groups of R1 or R2 are optionally substituted by from 1 to 3 substituents independently selected from the group consisting of:
- halogen;
- (C1-C6)alkyl;
- (C3-C8)cycloalkyl;
- (C4-C8)cycloalkenyl;
- (C1-C6)alkoxy;
- hydroxy;
- R12 CO2, R12R13NCO, R12R13N;
- (C1-C6)alkylcarbonyl, —CHO, cyano, thio;
- (C1-C6)alkylthio;
- (C1-C6)alkylsulfonyl;
- (C1-C6)alkylsulfinyl;
- hydroxy(C1-C6)alkyl;
- (C1-C6)alkoxycarbonylamino;
- (C1-C6)alkylcarbonylamino;
- (C1-C6)alkenylcarbonylamino;
- (C1-C6)alkoxycarbonyloxy;
- R12 R13 N(C1-C6);
- R12R13N(C1-C6)alkoxy;
- R12l R13N(C1-C6alkyl)S;
- N-morpholino(CH2)nO;
- or —R12R13N(CH2)nS(O)x;
- wherein the (C1-C6)alkyl;
- (C3-C8)cycloalkyl;
- (C4-C8)cycloalkenyl;
- (C1-C6)alkoxy;
- (C1-C6)alkylcarbonyl;
- (C1-C6)alkylthio;
- (C1-C6)alkylsulfonyl;
- (C1-C6)alkylsulfinyl;
- (C1-C6)alkoxycarbonylamino;
- (C1-C6)alkylcarbonylamino;
- (C1-C6)alkenylcarbonylamino;
- or (C1-C6)alkoxycarbonyloxy groups are each optionally further substituted by from 1 to 3 substituents independently selected from the group consisting of:
- halogen, (C1-C6)alkyl;
- (C3-C8)cycloalkyl;
- (C4-C8)cycloalkenyl;
- (C1-C6)alkoxy, hydroxy, R12 CO2, R12R13NCO, R12R13N;(C1-C6)alkylcarbonyl, —CHO, cyano, thio;
- R12 SO2(C1-C6)alkyl;
- R12 CO2(C1-C6)alkyl;
- R12R13NCO(C1-C6)alkyl;
- R12 CO(C1-C6)alkyl;
- R12 SO2(C1-C6)alkoxy;
- R12 CO2(C1-C6)alkoxy;
- R12R13NCO(C1-C6)alkoxy;
- R12CO(C1-C6)alkoxy;
- R12R13 N SO2(C1-C6)alkyl;
- and R12R13N SO2(C1-C6) alkoxy;
- wherein:
- R12 and R13 are each independently selected from the group consisting of hydrogen;
- (C1-C7)alkyl;
- (C3-C8)cycloalkyl;
- (C4-C8)cycloalkenyl;(C6-C10) aryl;
- (C2-C10)alkenyl, (C2-C10)alkynyl;
- (C2-C4)heteroaryl;
- (C1-C6)alkylaryl;
- (C1-C6) alkyl(C2-C6)heteroaryl;
- (C2-C6)alkoxyaryl;
- (C2-C6) alkoxy(C2-C6)heteroaryl;
- or R12 and R13 taken together form a three to eight membered heterocyclic ring having 1 to 3 heteroatoms;
- n is from 0 to 5;
- and x is 1 or 2;
- or R1 and R2 are each independently a group of the formula:
- 11
- wherein R7, R8 R10 and R11 are each independently hydrogen;
- hydroxy;
- (C1-C6) alkyl;
- (C1-C6)alkoxy;
- or halogen;
- R9 is hydroxy;
- (C1-C6) alkoxy;
- (C1-C6)alkoxycarbonyloxy;
- (C1-C6)alkylcarbonyloxy;
- (C3-C8)cycloalkoxy;
- (C4-C8)cycloalkenyloxy;
- or (C6-C12) aryloxy;
- and
- R3, R4, R5 and R6 are each independently hydrogen, hydroxy;
- (C1-C6)alkyl;
- (C1-C6)alkoxy;
- or halogen;
- with the proviso that at least one of R1 or R2 must be the group of formula (II)
90 more elements
A pharmaceutical composition for antagonizing or agonizing the estrogen receptor in a mammal comprising an estrogen receptor antagonizing or agonizing effective amount of a compound selected from the group consisting of:
- 4-(5-phenyl-2-trifluoromethyl-3H-imidazol-4-yl)-phenol;
- 4-[5-[(4-hydroxy-phenyl)2-trifluoromethyl-3-H-imidazol4-yl]-phenol;
- 4-[5-[(4-methoxy-phenyl)-2-trifluoromethyl-1H-imidazol-4-yl]-phenol;
- and 4-(4-phenyl-5-trifluoromethyl-isoxazol-3-yl)-phenol, or a pharmaceutically accepted salt thereof, and a pharmaceutically acceptable carrier.
1 more element
Dependencies are inferred from the claim text.