| 1224733-49-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• CAS: 1224733-49-6
• 化学式: C₂₃H₂₁F₇N₂O₂
• 分子量: 490.421
• InChiKey: AAMSRIRJJDBNAA-FXVNIEKYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.04
• 重原子数：
  34.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  55.56
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  (6R,7S,7aS)-2-azido-6-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-7-(4-fluorophenyl)hexahydro-3H-pyrrolizin-3-one 在 水 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 生成 、
  参考文献：
  名称：

  Substituted fused bicyclic pyrrolizinones as potent, orally bioavailable hNK1 antagonists

  摘要：

  Previous work on human NK1 (hNK(1)) antagonists in which the core of the structure is a 5,5-fused pyrrolizinone has been disclosed. The structural-activity-relationship studies on simple alpha- and beta-substituted compounds of this series provided several potent and bioavailable hNK1 antagonists that displayed excellent brain penetration as observed by their good efficacy in the gerbil foot-tapping (GFT) model assay. Several of these compounds exhibited 100% inhibition of the foot-tapping response at 0.1 and 24 h with ID50's of less than 1 mpk. One particular alpha-substituted compound (2b) had an excellent pharmacokinetic profile across preclinical species with reasonable in vivo functional activity and minimal ancillary activity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.065

文献信息

• Substituted fused bicyclic pyrrolizinones as potent, orally bioavailable hNK1 antagonists
  作者：Gregori J. Morriello、Sander G. Mills、Tricia Johnson、Mikhail Reibarkh、Gary Chicchi、Julie DeMartino、Marc Kurtz、P. Davies、K.L.C. Tsao、Song Zheng、Xinchun Tong、Emma Carlson、Karen Townson、F.D. Tattersall、Alan Wheeldon、Susan Boyce、Neil Collinson、Nadia Rupniak、Stephen Moore、Robert J. DeVita

  DOI：10.1016/j.bmcl.2010.01.065

  日期：2010.3

  Previous work on human NK1 (hNK(1)) antagonists in which the core of the structure is a 5,5-fused pyrrolizinone has been disclosed. The structural-activity-relationship studies on simple alpha- and beta-substituted compounds of this series provided several potent and bioavailable hNK1 antagonists that displayed excellent brain penetration as observed by their good efficacy in the gerbil foot-tapping (GFT) model assay. Several of these compounds exhibited 100% inhibition of the foot-tapping response at 0.1 and 24 h with ID50's of less than 1 mpk. One particular alpha-substituted compound (2b) had an excellent pharmacokinetic profile across preclinical species with reasonable in vivo functional activity and minimal ancillary activity. (C) 2010 Elsevier Ltd. All rights reserved.