tert-butyl (2R,3S,4R)-2-acetyl-4-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(4-fluorophenyl)pyrrolidine-1-carboxylate | 945467-56-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: tert-butyl (2R,3S,4R)-2-acetyl-4-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(4-fluorophenyl)pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (2R,3S,4R)-2-acetyl-4-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)pyrrolidine-1-carboxylate
• CAS: 945467-56-1
• 化学式: C₂₇H₂₈F₇NO₄
• 分子量: 563.512
• InChiKey: QQKVNGMQGVIDTN-IUBJVUOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  tert-butyl (2R,3S,4R)-2-acetyl-4-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(4-fluorophenyl)pyrrolidine-1-carboxylate 、 S-叔丁基亚磺酰胺 在 titanium(IV) tetraethanolate 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 以77%的产率得到tert-butyl (2R,3S,4R)-4-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-2-[(1E)-N-(tert-butylsulfinyl)ethanimidoyl]-3-(4-fluorophenyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  WO2007/87224

  摘要：

  公开号：
• 作为产物：
  描述：

  C₂₇H₃₀F₇NO₄ 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 生成 tert-butyl (2R,3S,4R)-2-acetyl-4-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(4-fluorophenyl)pyrrolidine-1-carboxylate
  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

• WO2007/87224
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.