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: | 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, Fobian, Steven E, Heasley, Jerry W, Cubbage, Joseph B, Moon, David L, Brown, Brad A, Acker, Todd M, Maddux, Mike B, Tollefson, Brent V, Mischke, Dafydd R, Owen, John N, Freskos, John M, Molyneaux, Alan G, Benson, Rhadika M, Blevis-Bal |
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| Rok vydání: | 2010 |
| Předmět: |
Cyclic Nucleotide Phosphodiesterases
Type 5 Male Dose-Response Relationship Drug Molecular Structure Phosphodiesterase Inhibitors Pyridines Administration Oral Biological Availability Brain Blood Pressure Phosphodiesterase 5 Inhibitors Rats Rats Sprague-Dawley Models Chemical Drug Design Pyrazines Rats Inbred SHR Animals Humans |
| Zdroj: | Journal of medicinal chemistry. 53(6) |
| ISSN: | 1520-4804 |
| 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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