(3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-(4-fluorophenyl)pyrrolidine | 849672-60-2

• 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: (3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-(4-fluorophenyl)pyrrolidine
• 英文别名: (3R,4S)-3-({(1R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethyl}oxy)-4-(4-fluorophenyl)pyrrolidine；(3R,4S)-3-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-4-(4-fluorophenyl)pyrrolidine
• CAS: 849672-60-2
• 化学式: C₂₀H₁₈F₇NO
• 分子量: 421.358
• InChiKey: ADJNVUFLQWHPMJ-AFBMGJRZSA-N

物化性质

• 沸点：
  369.0±42.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-(4-fluorophenyl)pyrrolidine 在 四(三苯基膦)钯 4 A molecular sieve 、 溴 、 对甲苯磺酸 、 三乙胺 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 19.25h， 生成 methyl 2-[(3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-(4-fluorophenyl) pyrrolidin-1-yl]-5-oxocyclopent-1-ene-1-carboxylate
  参考文献：
  名称：

  [EN] PHENYL PYRROLIDINE ETHER TACHYKININ RECEPTOR ANTAGONISTS
  [FR] ANTAGONISTES DU RECEPTEUR DE LA TACHYKININE A BASE DE PHENYLE PYRROLIDINE ETHER

  摘要：

  公开号：

  WO2005032464A3
• 作为产物：
  描述：

  tert-butyl (3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-(4-fluorophenyl)pyrrolidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-(4-fluorophenyl)pyrrolidine
  参考文献：
  名称：

  The discovery of potent, selective, and orally bioavailable hNK1 antagonists derived from pyrrolidine

  摘要：

  SAR studies on amides, ureas, and vinylogous amides derived from pyrrolidine led to the discovery of several potent hNK(1) antagonists. One particular vinylogous amide (45b) had excellent potency, selectivity, pharmacokinetic profile, and functional activity in vivo. An in vivo rhesus macaque brain receptor occupancy PET study for compound 45b revealed an estimated Occ(90) similar to 300 ng/ml. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.06.085

文献信息

• Phenyl pyrrolidine ether tachykinin receptor antagonists
  申请人：DeVita J. Robert

  公开号：US20070043015A1

  公开（公告）日：2007-02-22

  The present invention is directed to certain phenyl pyrrolidine ether compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, depression, and anxiety.

  本发明涉及某些苯基吡咯烷醚化合物，其作为神经激肽-1（NK-1）受体拮抗剂和快速激肽，特别是物质P的抑制剂具有用途。本发明还涉及包含这些化合物作为活性成分的制药配方以及这些化合物及其配方在治疗某些疾病，包括呕吐、抑郁和焦虑方面的应用。
• US7468437B2
  申请人：——

  公开号：US7468437B2

  公开（公告）日：2008-12-23
• [EN] PHENYL PYRROLIDINE ETHER TACHYKININ RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DU RECEPTEUR DE LA TACHYKININE A BASE DE PHENYLE PYRROLIDINE ETHER
  申请人：MERCK & CO INC

  公开号：WO2005032464A3

  公开（公告）日：2005-08-04
• The discovery of potent, selective, and orally bioavailable hNK1 antagonists derived from pyrrolidine
  作者：Peter Lin、Lehua Chang、Robert J. DeVita、Jonathan R. Young、Ronsar Eid、Xinchun Tong、Song Zheng、Richard G. Ball、Nancy N. Tsou、Gary G. Chicchi、Marc M. Kurtz、Kwei-Lan C. Tsao、Alan Wheeldon、Emma J. Carlson、WaiSi Eng、H. Donald Burns、Richard J. Hargreaves、Sander G. Mills

  DOI：10.1016/j.bmcl.2007.06.085

  日期：2007.9

  SAR studies on amides, ureas, and vinylogous amides derived from pyrrolidine led to the discovery of several potent hNK(1) antagonists. One particular vinylogous amide (45b) had excellent potency, selectivity, pharmacokinetic profile, and functional activity in vivo. An in vivo rhesus macaque brain receptor occupancy PET study for compound 45b revealed an estimated Occ(90) similar to 300 ng/ml. (c) 2007 Elsevier Ltd. All rights reserved.