7-chloro-3-[(1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one | 1233702-98-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 7-chloro-3-[(1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one
• CAS: 1233702-98-1
• 化学式: C₁₇H₂₂ClN₅O₂
• 分子量: 363.847
• InChiKey: GTVXRZQOZOTHHK-VXGBXAGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-chloro-3-[(1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one 、 2-甲氧基-5-吡啶硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 生成
  参考文献：
  名称：

  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)

  摘要：

  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.

  DOI：

  10.1021/jm901781q
• 作为产物：
  描述：

  3,7-dichloro-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one 、 (1R,4R)-2,5-二氮杂双环<2.2.1>庚烷 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 7-chloro-3-[(1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one
  参考文献：
  名称：

  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)

  摘要：

  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.

  DOI：

  10.1021/jm901781q

文献信息

• Design, Synthesis, and Biological Evaluation of 3-[4-(2-Hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-<i>b</i>]pyrazin-2(1<i>H</i>)-one, a Potent, Orally Active, Brain Penetrant Inhibitor of Phosphodiesterase 5 (PDE5)
  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. 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

  DOI：10.1021/jm901781q

  日期：2010.3.25

  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.