[(1R,2S,3S)-3-[(R)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-2-(4-fluoro-phenyl)-cyclopentyl]-(2-methoxy-ethyl)-amine | 190267-05-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(1R,2S,3S)-3-[(R)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-2-(4-fluoro-phenyl)-cyclopentyl]-(2-methoxy-ethyl)-amine
• 英文别名: (1R,2S,3S)-3-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-2-(4-fluorophenyl)-N-(2-methoxyethyl)cyclopentanamine；(1R,2S,3S)-3-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-2-(4-fluorophenyl)-N-(2-methoxyethyl)cyclopentan-1-amine
• CAS: 190267-05-1
• 化学式: C₂₄H₂₆F₇NO₂
• 分子量: 493.465
• InChiKey: SCTMGBDXYTYTJH-KAJMWERUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  [(1R,2S,3S)-3-[(R)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-2-(4-fluoro-phenyl)-cyclopentyl]-(2-methoxy-ethyl)-amine 、 2-碘乙酰胺 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 以57%的产率得到2-[[(1R,2S,3S)-3-[(R)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-2-(4-fluoro-phenyl)-cyclopentyl]-(2-methoxy-ethyl)-amino]-acetamide
  参考文献：
  名称：

  Cyclopentane-based human NK1 antagonists. Part 2: Development of potent, orally active, water-soluble derivatives

  摘要：

  The synthesis and optimization of a cyclopentane-based hNK1 antagonist scaffold 3, having four chiral centers, will be discussed in the context of its enhanced water-solubility properties relative to the marketed anti-emetic hNK1 antagonist EMEND (R) (Aprepitant). Sub-nanomolar hNK1 binding was achieved and oral activity comparable to Aprepitant in two in vivo models will be described. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.06.044
• 作为产物：
  描述：

  (1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl 2,2,2-trichloroethanimidate 在 palladium on activated charcoal 4-二甲氨基吡啶 、 sodium hydroxide 、 tetrafluoroboric acid 、 sodium azide 、 草酰氯 、 氢气 、 sodium hydride 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 生成 [(1R,2S,3S)-3-[(R)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-2-(4-fluoro-phenyl)-cyclopentyl]-(2-methoxy-ethyl)-amine
  参考文献：
  名称：

  Cyclopentane-based human NK1 antagonists. Part 2: Development of potent, orally active, water-soluble derivatives

  摘要：

  The synthesis and optimization of a cyclopentane-based hNK1 antagonist scaffold 3, having four chiral centers, will be discussed in the context of its enhanced water-solubility properties relative to the marketed anti-emetic hNK1 antagonist EMEND (R) (Aprepitant). Sub-nanomolar hNK1 binding was achieved and oral activity comparable to Aprepitant in two in vivo models will be described. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.06.044

文献信息

• USE OF NEUROKININ-1 ANTAGONISTS AS ANTITUSSIVES
  申请人：Menlo Therapeutics Inc.

  公开号：US20180235931A1

  公开（公告）日：2018-08-23

  The disclosure relates to the use of neurokinin-1 (NK-1) antagonists, such as serlopitant, MK-0303 or MK-8478, in alleviating or suppressing cough (including acute, subacute and chronic cough) and urge to cough. The cough can have an unknown cause (idiopathic cough) or can be associated with any type of medical condition, such as a respiratory disorder. The NK-1 antagonist can be delivered by oral inhalation for more rapid peripheral and central antitussive action. Another antitussive agent in addition to the NK-1 antagonist can optionally be administered for the treatment of the cough or urge to cough, or the cough-associated medical condition.
• US5750549A
  申请人：——

  公开号：US5750549A

  公开（公告）日：1998-05-12
• Cyclopentane-based human NK1 antagonists. Part 2: Development of potent, orally active, water-soluble derivatives
  作者：Laura C. Meurer、Paul E. Finke、Karen A. Owens、Nancy N. Tsou、Richard G. Ball、Sander G. Mills、Malcolm MacCoss、Sharon Sadowski、Margaret A. Cascieri、Kwei-Lan Tsao、Gary G. Chicchi、Linda A. Egger、Silvi Luell、Joseph M. Metzger、D. Euan MacIntyre、Nadia M.J. Rupniak、Angela R. Williams、Richard J. Hargreaves

  DOI：10.1016/j.bmcl.2006.06.044

  日期：2006.9

  The synthesis and optimization of a cyclopentane-based hNK1 antagonist scaffold 3, having four chiral centers, will be discussed in the context of its enhanced water-solubility properties relative to the marketed anti-emetic hNK1 antagonist EMEND (R) (Aprepitant). Sub-nanomolar hNK1 binding was achieved and oral activity comparable to Aprepitant in two in vivo models will be described. (c) 2006 Elsevier Ltd. All rights reserved.