Treating erectile dysfunction using new or known imidazo(1,5-a)pyrido(3,2-e)pyrazinone derivatives, as cGMP-selective phosphodiesterase V inhibitors free of cardiovascular side-effects

摘要

The use of 1,3-dialkyl-8-alkoxy-5-(substituted methyl)-imidazo[1,5-a]pyrido[3,2-e]pyrazinones (I) for treating erectile dysfunction is new. (I) include new 5-(cyclohexylmethyl) compounds. The use of imidazo-pyrido-pyrazinone compounds of formula (I), or their addition salts with inorganic or organic acids or bases or quaternary ammonium salt derivatives, is claimed as therapeutic agents for the preparation of medicaments for treating erectile dysfunction (impotence). [Image] R1, R2, R41-4C alkyl; R3CH2A; A : cyclohexyl, 6-10C mono- or bicyclic aryl (optionally substituted by one or more of F, Cl, Br, NO2, OH, OMe, Me or CN), or mono- or bicyclic heteroaryl containing 3-10C and 1-4 heteroatoms (preferably N, S or O) (optionally substituted by one or more of F, Cl, Br, NO2, OH, OMe, Me or CN). An independent claim is also included for compounds (I; A = cyclohexyl). - ACTIVITY : Vasotropic; Relaxant. - MECHANISM OF ACTION : Phosphodiesterase-V (PDE V) inhibitor; Increase of nitrogen monoxide induced intracellular cyclic guanosine monophosphate (cGMP) levels in the corpus cavernosum; Relaxation of smooth muscle of the corpus cavernosum. 1-Ethyl-8-methoxy-3-methyl-4-(4-pyridylmethyl)-imidazo[1, 5-a]pyrido[3,2-e]pyrazinone hydrochloride (Ia) displayed an IC50 value of 0.002 MicroM for inhibition of PDE V. [Image]