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(1H)-one, a Potent, Orally Active,

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• 作者：Robert O. Hughes ; D. Joseph Rogier ; E. Jon Jacobsen ; John K. Walker ; Alan MacInnes ; Brian R. Bond ; Lena L. Zhang ; Ying Yu ; Yi Zheng ; Jeanne M. Rumsey ; Jennie L. Walgren ; Sandra W. Curtiss ; Yvette M. F
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：March 25, 2010
• 年：2010
• 卷：53
• 期：6
• 页码：2656-2660
• 全文大小：783K
• 年卷期：v.53,no.6(March 25, 2010)
• ISSN：1520-4804

文摘

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(1H)-one, which possessed an excellent potency and selectivity profile and demonstrated robust in vivo blood pressure lowering in a spontaneously hypertensive rat (SHR) model. Furthermore, this compound is brain penetrant and will be a useful agent for evaluating the therapeutic potential of central inhibition of PDE5. This compound has recently entered clinical trials.