Novel pyrazolopyrimidopyridazinones with potent and selective phosphodiesterase 5 (PDE5) inhibitory activity as potential agents for treatment of erec...
Basic Information
ID: ALA1146047
Journal: J Med Chem
Title: Novel pyrazolopyrimidopyridazinones with potent and selective phosphodiesterase 5 (PDE5) inhibitory activity as potential agents for treatment of erectile dysfunction.
Authors: Giovannoni MP, Vergelli C, Biancalani C, Cesari N, Graziano A, Biagini P, Gracia J, Gavaldà A, Dal Piaz V.
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.
CiteXplore: 16913726
DOI: 10.1021/jm060265+
Patent ID: ┄