Details for Patent: 6,608,065

Title:	Use of cGMP phosphodiesterase inhibitors in methods to treat female sexual dysfunction
Abstract:	The use of (6R, 12aR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)-pyraz ino[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)py razino[2', 1':6,1]pyrido[3,4-b]indole-1,4-dione, and physiologically acceptable salts and solvates thereof, in the treatment of impotence.
Inventor(s):	Daugan; Alain Claude-Marie (Les Ulis, FR)
Assignee:	ICOS Corporation (Bothell, WA)
Filing Date:	May 18, 2000
Application Number:	09/573,905
Claims:	1. A method for the treatment of female sexual dysfunction related to clitoral disturbances, comprising administration of a PDEV inhibitor of formula (I): ##STR6## and salts and solvates (e.g., hydrates) thereof, in which: R.sup.0 represents hydrogen, halogen, or C,.sub.1-6 alkyl; R.sup.1 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, haloC.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkyl C.sub.1-3 alkyl, arylC.sub.1-3 alkyl, or heteroarylC.sub.1-3 alkyl; R.sup.2 represents an optionally substituted monocyclic aromatic ring selected from benzene, thiophene, furan, and pyridine or an optionally substituted bicyclic ring ##STR7## 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 R.sup.3 represents hydrogen or C.sub.1-3 alkyl, or R.sup.1 and R.sup.3 together represent a 3- or 4-membered alkyl or alkenyl chain. 2. The method of claim 1 wherein the compound of formula (I) is administered orally. 3. The method of claim 1 wherein the sexual dysfunction is an orgasmic dysfunction. 4. 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-methylenedioxypheny l)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-methylpyra zino[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-methylenedioxypheny l)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)p yrazino[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-methylpyr azino[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)pyr azino[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)py rrolo[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)pyra zino[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. 5. A method of claim 4 wherein the compound is administered orally. 6. 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)pyr azino[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-methylenedioxyphe nyl)pyrazino[2', 1':6,1]pyrido[3,4-b]indole-1,4-dione; and physiologically acceptable salts and solvates thereof. 7. The method of claim 6 wherein the compound is administered orally. 8. 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-methylenedioxypheny l)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-methylpyra zino[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-methylenedioxypheny l)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)p yrazino[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-methylpyr azino[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)pyr azino[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)p yrrolo[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)pyra zino[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.