cGMP-PDE inhibitors for the treatment of erectile dysfunction

Abstract

Pyrazolopyrimidine compounds which are selective inhibitors of cGMP PDE are useful in the treatment of erectile dysfunction (impotence) in male animals, including man.

1 . The use of a compound which is a selective cGMP PDE inhibitor for the manufacture of a medicament for the treatment of erectile dysfunction in a male animal, including man, wherein said compound is: 
 i a 5-substituted pyrazolo[4,3-d]pyrimdine-7-one as disclosed in European patent application 0201188;    ii a griseolic acid derivative as disclosed in European patent applications nos 0214708 and 0319050;    iii a 2-phenylpurinone derivative as disclosed in European patent application 0293063;    iv a phenylpyridone derivative as disclosed in European patent application 0347027;    v a fused pyrimidine derivative as disclosed in European patent application 0347146;    vi a condensed pyrimidine derivative as disclosed in European patent application 0349239;    vii a pyrimidopyrimidine derivative as disclosed in European patent application 0351058;    viii a purine compound as disclosed in European patent application 0352960;    ix a quinazolinone derivative as disclosed in European patent application 0371731;    x a phenylpyrimidone derivative as disclosed in European patent application 0395328;    xi an imidazoquinoxalinone derivative or its aza analogue as disclosed in European patent application 0400583;    xii a phenylpyrimidone derivative as disclosed in European patent application 0400799;    xiii a phenylpyridone derivative as disclosed in European patent application 0428268;    xiv a pyrimidopyrimidine derivative as disclosed in European patent 0442204;    xv a 4-aminoquinazoline derivative as disclosed in European patent application 0579496;    xvi a 4,5-dihydro4-oxo-pyrrolo[1,2-a]quinoxaline derivative or its aza analogue as disclosed in European patent application 0584487;    xvii a polycyclic guanine derivative as disclosed in International patent application WO91/19717;    xviii a nitrogenous heterocyclic compound as disclosed in International patent application WO93/07124;    xix a 2-benzyl-polycyclic guanine derivative as disclosed in International patent application WO 94/19351;    xx a quinazoline derivative as disclosed in U.S. Pat. No. 4,060,615    xxi a 6-heterocyclyl pyrazolo[3,4-d]pyrimidin-4-one as disclosed in U.S. Pat. No. 5,294,612    xxii a benzimidazole as disclosed in Japanese patent application 5-222000; or xxiii a cycloheptimidazole as disclosed in European Journal of Pharmacology, 251, (1994), 1.    xxiv a N-containing heterocycle as disclosed in International patent application WO94/22855.    
     
     
         2 . The use of a compound as claimed in  claim 1  wherein said compound is: 
 a 4-aminoquinazoline derivative as disclosed in European patent application 0579496;  
 a nitrogenous heterocyclic compound as disclosed in International patent application WO93/07124;  
 a 6-heterocyclyl pyrazolo[3,4-d]pyrimid-4-one as disclosed in U.S. Pat. No. 5,294,612 or  
 a N-containing heterocycle as disclosed in International patent application WO94/22855.  
 
     
     
         3 . The use of a compound as claimed in  claim 1  wherein said compound is: 
 1,3-dimethyl-5-benzylpyrazolo[4,3-d]pyrimidine-7-one;  
 2-(2-propoxyphenyl)-6-purinone;  
 6-(2-propoxyphenyl)-1,2-dihydro-2-oxopyridine-3-carboxamide;  
 2-(2-propoxyphenyl)pyrido[2,3-d]pyrimid4(3H)-one;  
 7-methylthio-4-oxo-2-(2-propoxyphenyl)-3,4-dihydropyrimido[4,5-d]pyrimidine;  
 6-hydroxy-2-(2-propoxyphenyl)pyrimidine-4-carboxamide;  
 1-ethyl-3-methylimidazo[1,5a]quinoxalin-4(5H)-one;  
 4-phenylmethylamino-6-chloro-2-(1-imidazoloyl)quinazoline;  
 5-ethyl-8-[3-(N-cyclohexyl-N-methylcarbamoyl)-propyloxy]-4,5-dihydro4-oxo-pyrido[3,2-e]pyrrolo[1,2-a]pyrazine;  
 5′-methyl-3′-(phenylmethyl)-spiro[cyclopentane-1,7′(8′H)-(3′H)-imidazo[2,1-b]purin]4′(5′H)-one  
 1-[6-chloro-4-(3,4-methylenedioxybenzyl)aminoquinazolin-2-yl)piperidine4-carboxylic acid;  
 (6aR,9aS)-2-(4-trifluoromethylphenyl)methyl-5-methyl-3,4,5,6a,7,8,9,9a-octahydrocyclopent[4,5]imidazo[2,1-b]purin-4-one;  
 1-tert-butyl-3-phenylmethyl-6-(4-pyridyl)pyrazolo[3,4-d]pyrimid-4-one;  
 1-cyclopentyl-3-methyl-6-(4-pyridyl)4,5-dihydro- 1H-pyrazolo[3,4-d]pyrimid4-one;  
 2-butyl-1-(2-chlorobenzyl)6-ethoxycarbonylbenzimidazole;  
 2-(4-carboxypiperidino)-4-(3,4-methylenedioxybenzyl)amino-6-nitroquinazoline; or 2-phenyl-8-ethoxycycloheptimidazole.  
 
     
     
         4 . The use of a compound as claimed in  claim 3  where said compound is: 
 4-phenylmethylamino-6-chloro-2-(1-imidazoloyl)quinazoline;  
 1-[6-chloro-4-(3,4-methylenedioxybenzyl)aminoquinazolin-2-yl)piperidine-4-carboxylic acid;  
 (6aR,9aS)-2-(4-trifluoromethylphenyl)methyl-5-methyl-3,4,5,6a,7,8,9,9a-octahydrocyclopent[4,5]imidazo[2,1-b]purin-4-one;  
 1-tert-butyl-3-phenylmethyl-6-(4-pyridyl)pyrazolo[3,4-d]pyrimid4-one;  
 1-cyclopentyl-3-methyl-6-(4-pyridyl)4 ,5-dihydro-1H-pyrazolo[3,4-d]pyrimid-4-one; or  
 2-(4-carboxypiperidino)-4-(3,4-methylenedioxybenzyl)amino-6-nitroquinazoline;  
 
     
     
         5 . The use of a compound which is a selective cGMP PDE inhibitor for the manufacture of a medicament for the treatment of erectile dysfunction in a male animal, including man, wherein said compound is: 
 xxv a pyrazolopyrimidine derivative as disclosed in European patent application 0636626;    xxvi a 4-aminopyrimidine derivative as disclosed in European patent application 0640599;    xxvii a imidazoquinazoline derivative as disclosed in International patent application WO95/06648;    xxviii an anthranilic acid derivative as disclosed in International patent application WO95/18097;    xxix a 4-aminoquinazoline derivative as disclosed in U.S. Pat. No. 5,436,233;    xxx a tetracyclic derivative as disclosed in International patent application WO95/19978;    xxxi a imidazoquinazoline derivative as disclosed in European patent application 0668280; or    xxxii a quinazoline compound as disclosed in European patent application 0669324.    
     
     
         6 . The use of a compound which is a selective cGMP PDE inhibitor for the manufacture of a medicament for the curative or prophylactic treatment of female sexual dysfunction, premature labour or dysmenorrhea, wherein said compound is a compound as previously claimed in any one of  claims 1  to  5  for use in the treatment of erectile dysfunction in a male.  
     
     
         7 . A method for the treatment of erectile dysfunction in a male animal or female sexual dysfunction, premature labour or dysmenorrhea, which comprises administering an effective amount of a compound which is a selective cGMP PDE inhibitor as previously claimed in any one of  claims 1  to  5 .