SILDENAFIL (VIAGRA~), A POTENT AND SELECTIVE INHIBITOR OF TYPE 5 CGMP PHOSPHODIESTERASE WITH UTILITY FOR THE TREATMENT OF

Abstract: 5-(2'-Alkoxyphenyl)pyrazolo[4,3-d]pyrimidin-7-ones, and i particular our preferred compound, sildenafil (VIAGRAa'M), discovered through a rational drug design programme, are potent and selective inhibitors of the type 5 cGMP phosphodiesterase from both rabbit platelets and haman corpus cavernosum. Sildenafil s currently in the clinic for the oral treatment ofmale erectile dysfunction. Copyright © 1996 Elsevier Science Ltd Introduction: Cyclic guanosine monophosphate (cGMP) is the ubiquitous econd messenger for those G-protein coupled receptors activated by endogenous substances such as nitric oxide (NO or EDRF) and atrial natriuretic peptide (ANP). Intracellular levels of cGMP are controlled by activation of cyclic nucleotide cyclases and breakdown by phosphodiesterases (PDE). Specifically, there are a number of PDE isozymes that will hydrolyse cGMP to the inactive GMP and thus cGMP levels may be raised by the use of a selective cGM