Substituted Pyrazolopyridopyridazines as Orally Bioavailable Potent and Selective PDE5 Inhibitors: Potential Agents for Treatment of Erectile Dysfunction
Journal of Medicinal Chemistry2003Vol. 46(4), pp. 457–460
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Guixue Yu, Helen J. Mason, Ximao Wu, Jian Wang, Saeho Chong, Bruce Beyer, Andrew Henwood, Ronald Pongrac, Laurie Seliger, Bin He, Diane E. Normandin, Pam Ferrer, Rongan Zhang, Leonard P. Adam, William G. Humphrey, John Krupinski, John E. Macor
Abstract
Novel pyrazolopyridopyridazine derivatives have been prepared as potent and selective PDE5 inhibitors. Compound 6 has been identified as a more potent and selective PDE5 inhibitor than sildenafil (1). It is as efficacious as sildenafil in in vitro and in vivo PDE5 inhibition models, and it is orally bioavailable in rats and dogs. The superior isozyme selectivity of 6 is expected to exert less adverse effects in humans when used for erectile dysfunction treatment.
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