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, Brain Penetrant Inhibitor of Phosphodiesterase 5 (PDE5)

Autor:	Sandra W. Curtiss, D. Joseph Rogier, Alan MacInnes, Brown David L, Mike B. Tollefson, Brian R. Bond, Yvette M. Fobian, Maddux Todd Michael, Dafydd R. Owen, Jeanne M. Rumsey, Brent V. Mischke, Jerry W. Cubbage, Alan G. Benson, Robert Hughes, Lena L Zhang, E. Jon Jacobsen, Steven E. Heasley, Joseph B. Moon, Ying Yu, John M. Molyneaux, Yi Zheng, Brad A. Acker, Blevis-Bal Radhika M, John N. Freskos, John K. Walker, Jennie L. Walgren
Rok vydání:	2010
Předmět:	Stereochemistry Chemistry Pharmacology chemistry.chemical_compound Spontaneously hypertensive rat Orally active Design synthesis In vivo cGMP-specific phosphodiesterase type 5 Drug Discovery Molecular Medicine Potency Penetrant (biochemical) Biological evaluation
Zdroj:	Journal of Medicinal Chemistry. 53:2656-2660
ISSN:	1520-4804 0022-2623
Popis:	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.
Databáze:	OpenAIRE
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