ABSTRACT
Twelve new pyrazolo [3, 4-d] pyriniidin-4-[5H]-one derivatives 13a-g, 14-17 and 24 were synthesized as inhibitors of phosphodiesterase enzyme type 5 [PDE5]. All intermediates and final compounds were analyzed by IR, H-NMR, mass spectra and elemental analysis. The title compounds were evaluated for their inhibitory activity toward PDE5 in comparison with sildenafil using anaesthetized normotensive rabbits. Eleven of the final compounds 13 a-g, 14, 16 and 24 were subjected to biological screening using animal model and nine of these compounds were subjected to molecular modeling study in order to investigate their binding mode. Most of the explored tested compounds showed the same binding mechanism as vardenafil and some of these compounds showed promising activity in comparison to sildenafil in the pharmacological studies. The results indicated that compound 24 is the most active member of the investigated series