Design, Synthesis, and Biological Evaluation of 3-[4-(2-Hydroxyethyl) piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl) pyrido [3, 4-b] pyrazin-2 (1 H)-one, a …

…, EJ Jacobsen, JK Walker, A MacInnes…

Index: Hughes, Robert O.; Rogier, D. Joseph; Jacobsen, E. Jon; Walker, John K.; Maclnnes, Alan; Bond, Brian R.; Zhang, Lena L.; Yu, Ying; Zheng, Yi; Rumsey, Jeanne M.; Walgren, Jennie L.; Curtiss, Sandra W.; Fobian, Yvette M.; Heasley, Steven E.; Cubbage, Jerry W.; Moon, Joseph B.; Brown, David L.; Acker, Brad A.; Maddux, Todd M.; Tollefson, Mike B.; Mischke, Brent V.; Owen, Dafydd R.; Freskos, John N.; Molyneaux, John M.; Benson, Alan G.; Blevis-Ba, Rhadika M. Journal of Medicinal Chemistry, 2010 , vol. 53, # 6 p. 2656 - 2660

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Citation Number: 11

Abstract

We recently described a novel series of aminopyridopyrazinones as PDE5 inhibitors. Efforts toward optimization of this series culminated in the identification of 3-[4-(2-hydroxyethyl) piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl) pyrido [3, 4-b] pyrazin-2 (1 H)- one, which possessed an excellent potency and selectivity profile and demonstrated robust in vivo blood pressure lowering in a spontaneously hypertensive rat (SHR) model. ...