Use of cGMP phosphodiesterase inhibitors in methods to treat female sexual dysfunction
AssigneeICOS Corporation
InventorAlain Claude-Marie Daugan
Life of this patent
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Abstract
The use of (6R, 12aR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)-pyrazino[2′,1′:6,1]pyrido[3,4-b]indole -1,4-dione, (3S, 6R, 12aR)-2,3,6,7,12,12a-hexahydro-2,3-dimethyl-6-(3,4-methylenedioxyphenyl)pyrazino[2′, 1′:6,1]pyrido[3,4-b]indole-1,4-dione, and physiologically acceptable salts and solvates thereof, in the treatment of impotence.
Claims8
A method for the treatment of female sexual dysfunction related to clitoral disturbances, comprising administration of a PDEV inhibitor of formula (I):
- and salts and solvates (e.g., hydrates) thereof, in which:
- R0 represents hydrogen, halogen, or C,1-6alkyl;
- R1 represents hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, haloC1-6alkyl, C3-8cycloalkyl, C3-8cycloalkyl C1-3alkyl, arylC1-3alkyl, or heteroarylC1-3alkyl;
- R2 represents an optionally substituted monocyclic aromatic ring selected from benzene, thiophene, furan, and pyridine or an optionally substituted bicyclic ring
- attached to the rest of the molecule via one of the benzene ring carbon atoms and wherein the fused ring A is a 5- or 6-membered ring which can be saturated or partially or fully unsaturated and comprises carbon atoms and optionally one or two heteroatoms selected from oxygen, sulphur, and nitrogen;
- and
- R3 represents hydrogen or C1-3alkyl, or R1 and R3 together represent a 3- or 4-membered alkyl or alkenyl chain.
A method for the treatment of female sexual dysfunction related to clitoral disturbances, comprising administration of a PDEV inhibitor selected from the group consisting of
- cis-2,3,6,7,12,12a-hexahydro-2-(4-pyridylmethyl)-6-(3,4-methylenedioxyphenyl)pyrazino[2′, 1′:6,1]pyrido[3,4-b]-indole-1,4-dione;
- cis-2,3,6,7,12,12a-hexahydro-6-(2,3-dihydrobenzo[b]furan-5-yl)-2-methylpyrazino[2′, 1′:6,1]pyrido[3,4-b]indole-1,4-dione;
- cis-2,3,6,7,12,12a-hexahydro-6-(5-bromo-2-thienyl)-2-methylpyrazino[2′, 1′:6,1]pyrido[3,4-b]indole-1,4-dione;
- cis-2,3,6,7,12,12a-hexahydro-2-butyl-6-(4-methylphenyl)-pyrazino[2′, 1′:6,1]pyrido[3,4-b]indole-1,4-dione;
- (6R,12aR)-2,3,6,7,12,12a-hexahydro-2-isopropyl-6-(3,4-methylenedioxyphenyl)pyrazino[2′, 1′:6,1]pyrido[3,4-b]-indole-1,4-dione;
- (6R,12aR)-2,3,6,7,12,12a-hexahydro-2-cyclopentyl-6-(3,4-methylenedioxyphenyl)pyrazino[2′, 1′:6,1]pyrido[3,4-b]-indole-1,4-dione;
- (6R,12aR)-2,3,6,7,12,12a-hexahydro-2-cyclopropylmethyl-6-(4-methoxyphenyl)pyrazino[2′,1′1:6,1]pyrido[3,4-b]indole-1,4-dione;
- (6R,12aR)-2,3,6,7,12,12a-hexahydro-6-(3-chloro-4-methoxyphenyl)-2-methylpyrazino[2′, 1′:6,1]pyrido[3,4-b]indole-1,4-dione;
- (6R,12aR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)pyrazino[2′, 1′:6,1]pyrido[3,4-b]-indole-1,4-dione;
- (6R,12aR)-2,3,6,7,12,12a-hexahydro-6-(2,4-methylenedioxyphenyl)pyrazino[2′, 1′:6,1]pyrido[3,4-b]indole-1,4-dione;
- (5a,12R,14aS)-1,2,3,5,6,11,12,14a-octahydro-12-(3,4-methylenedioxyphenyl)pyrrolo[1″,2″:4′,5′]pyrazino-[2′, 1′:6,1]pyrido[3,4-b]indole-5-1,4-dione;
- cis-2,3,6,7,12,12a-hexahydro-2-cyclopropyl-6-(3,4-methylenedioxyphenyl)pyrazino[2′, 1′:6,1]pyrido[3,4-b]indole-1,4-dione;
- (3S,6R,12aR)-2,3,6,7,12,12a-hexahydro-3-methyl-6-(3,4-methylenedioxyphenyl)pyrazino[2′, 1′:6,1]pyrido[3,4-b]-indole-1,4-dione;
- and physiologically acceptable salts and solvates thereof.
A method for the treatment of female/sexual dysfunction related to clitoral disturbances, comprising administration of a PDEV inhibitor selected from the group consisting of
- (6R,12aR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)pyrazino[2′, 1′:6,1]pyrido[3,4-b]-indole-1,4-dione;
- (3S,6R,12aR)-2,3,6,7,12,12a-hexahydro-2,3-dimethyl-6-(3,4-methylenedioxyphenyl)pyrazino[2′, 1′:6,1]pyrido[3,4-b]indole-1,4-dione;
- and physiologically acceptable salts and solvates thereof.
A method of treating a female animal for sexual dysfunction related to clitoral disturbances which comprises treating said female animal with an effective amount of a pharmaceutical composition comprising a PDEV inhibitor selected from the group consisting of
- cis-2,3,6,7,12,12a-hexahydro-2-(4-pyridylmethyl)-6-(3,4-methylenedioxyphenyl)pyrazino[2′, 1′:6,1]pyrido[3,4-b]-indole-1,4-dione;
- cis-2,3,6,7,12,12a-hexahydro-6-(2,3-dihydrobenzo[b]furan-5-yl)-2-methylpyrazino[2′, 1′:6,1]pyrido[3,4-b]indole-1,4-dione;
- cis-2,3,6,7,12,12a-hexahydro-6-(5-bromo-2-thienyl)-2-methylpyrazino[2′,1′:6,1]pyrido[3,4-b]indole-1,4-dione;
- cis-2,3,6,7,12,12a-hexahydro-2-butyl-6-(4-methylphenyl)-pyrazino[2′, 1′:6,1]pyrido[3,4-b]indole-1,4-dione;
- (6R,12aR)-2,3,6,7,12,12a-hexahydro-2-isopropyl-6-(3,4-methylenedioxyphenyl)pyrazino[2′,1′:6,1]pyrido[3,4-b]-indole-1,4-dione;
- (6R,12aR)-2,3,6,7,12,12a-hexahydro-2-cyclopentyl-6-(3,4-methylenedioxyphenyl)pyrazino[2′, 1′:6,1]pyrido[3,4-b]-indole-1,4-dione;
- (6R,12aR)-2,3,6,7,12,12a-hexahydro-2-cyclopropylmethyl-6-(4-methoxyphenyl)pyrazino[2′, 1′:6,1]pyrido[3,4-b]indole-1,4-dione;
- (6R,12aR)-2,3,6,7,12,12a-hexahydro-6-(3-chloro-4-methoxyphenyl)-2-methylpyrazino[2′,1′:6,1]pyrido[3,4-b]-indole-1,4-dione;
- (6R,12aR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)pyrazino[2′, 1′:6,1]pyrido[3,4-b]-indole-1,4-dione;
- (6R,12aR)-2,3,6,7,12,12a-hexahydro-6-(3,4-methylenedioxyphenyl)pyrazino[2′,1′:6,1]pyrido[3,4-b]indole-1,4-dione;
- (5aR,12R,14aS)-1,2,3,5,6,11,12,14a-octahydro-12-(3,4-methylenedioxyphenyl)pyrrolo[1″,2″:4′,5′]pyrazino-[2′, 1′:6,1]pyrido[3,4-b]indole-5-1,4-dione;
- cis-2,3,6,7,12,12a-hexahydro-2-cyclopropyl-6-(3,4-methylenedioxyphenyl)pyrazino[2′,11:6,1]pyrido[3,4-b]-indole-1,4-dione;
- (3S,6R,12aR)-2,3,6,7,12,12a-hexahydro-3-methyl-6-(3,4-methylenedioxyphenyl)pyrazino[2′,1′:6,1]pyrido[3,4-b]-indole-1,4-dione;
- and physiologically acceptable salts and solvates thereof, together with a pharmaceutically acceptable diluent or carrier.
Dependencies are inferred from the claim text.