Pyrazolo[1',5':1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones and their analogues, potentially useful for the treatment of erectile dysfunction, were synthesized and evaluated as inhibitors of phosphodiesterase 5 (PDE5). Several compounds showed IC50 values in the low nanomolar range, and in particular, compound 5r, displaying high potency toward PDE5 (IC50 ) 8.3 nM) and high selectivity versus PDE6 (240-fold) appeared to be a very promising new lead both in comparison with the potent but not selective sildenafil and in comparison with some analogues previously reported by us. SAR studies in this triheterocyclic scaffold led us to conclude that the best arranged groups are a methyl in position 1, a benzyl in position 3, a phenyl in position 9, and a linear four-carbon chain in position 6.

Novel pyrazolopyrimidopyridazinones with potent and selective phosphodiesterase 5 (PDE5) inhibitory activity agents as potential agents for treatment of erectile dysfunction / M.GIOVANNONI; C.VERGELLI; C.BIANCALANI; N.CESARI; A.GRAZIANO; P.BIAGINI; J.GRACIA; A.GAVALDA';V.DAL PIAZ. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - ELETTRONICO. - 49:(2006), pp. 5363-5371.

Novel pyrazolopyrimidopyridazinones with potent and selective phosphodiesterase 5 (PDE5) inhibitory activity agents as potential agents for treatment of erectile dysfunction

GIOVANNONI, MARIA PAOLA;VERGELLI, CLAUDIA;
2006

Abstract

Pyrazolo[1',5':1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones and their analogues, potentially useful for the treatment of erectile dysfunction, were synthesized and evaluated as inhibitors of phosphodiesterase 5 (PDE5). Several compounds showed IC50 values in the low nanomolar range, and in particular, compound 5r, displaying high potency toward PDE5 (IC50 ) 8.3 nM) and high selectivity versus PDE6 (240-fold) appeared to be a very promising new lead both in comparison with the potent but not selective sildenafil and in comparison with some analogues previously reported by us. SAR studies in this triheterocyclic scaffold led us to conclude that the best arranged groups are a methyl in position 1, a benzyl in position 3, a phenyl in position 9, and a linear four-carbon chain in position 6.
2006
49
5363
5371
M.GIOVANNONI; C.VERGELLI; C.BIANCALANI; N.CESARI; A.GRAZIANO; P.BIAGINI; J.GRACIA; A.GAVALDA';V.DAL PIAZ
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/316687
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