((1R),(2R),(3S))-3-((1R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-2-(4-fluorophenyl)cyclopentane-carboxylic acid | 405512-86-9

• 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),(2R),(3S))-3-((1R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-2-(4-fluorophenyl)cyclopentane-carboxylic acid
• 英文别名: 2alpha-(4-Fluorophenyl)-3beta-[[(R)-alpha-methyl-3,5-bis(trifluoromethyl)benzyl]oxy]cyclopentane-1beta-carboxylic acid；(1R,2R,3S)-3-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-2-(4-fluorophenyl)cyclopentane-1-carboxylic acid
• CAS: 405512-86-9
• 化学式: C₂₂H₁₉F₇O₃
• 分子量: 464.38
• InChiKey: VETUVXFSPPFPDP-QJJJLASOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  ((1R),(2R),(3S))-3-((1R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-2-(4-fluorophenyl)cyclopentane-carboxylic acid 在 palladium on activated charcoal 4-二甲氨基吡啶 、 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 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
• 作为产物：
  描述：

  methyl (1R,2R,3S)-2-(4-fluorophenyl)-3-hydroxycyclopentane-1-carboxylate 在 sodium hydroxide 、 三氟甲磺酸 作用下， 以 甲醇 、 二氯甲烷 、 环己烷 为溶剂， 生成 ((1R),(2R),(3S))-3-((1R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-2-(4-fluorophenyl)cyclopentane-carboxylic acid
  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

• Lactam tachykinin receptor antagonists
  申请人：Finke E. Paul

  公开号：US20050282886A1

  公开（公告）日：2005-12-22

  The present invention is directed to certain lactam 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, urinary incontinence, depression, and anxiety.

  本发明涉及某些内酰胺化合物，其可用作神经激肽-1（NK-1）受体拮抗剂，以及缓激肽和特别是P物质的抑制剂。该发明还涉及包含这些化合物作为活性成分的药物配方，以及在治疗某些疾病，包括呕吐、尿失禁、抑郁症和焦虑症中使用这些化合物及其配方。
• Combination Therapy for the Treatment of Urinary Frequency, Urinary Urgency and Urinary Incontinence
  申请人：Gottesdiener Keith M.

  公开号：US20090270406A1

  公开（公告）日：2009-10-29

  This invention concerns compositions for the treatment of urinary frequency, urinary urgency and urinary incontinence comprising (R)-N-[4-[2-[[2-hydroxy-2-(pyridin-3-yl)ethyl]amino]ethyl]phenyl]-4-[4-(4-tri-fluoromethylphenyl)thiazol-2-yl]benzenesulfonamide and pharmaceutically acceptable salts thereof. In another aspect, this invention concerns combination therapy for urinary frequency, urinary urgency and urinary incontinence wherein one of the active agents is (R)-N-[4-[2-[[2-hydroxy-2-(pyridin-3-yl)ethyl]amino]ethyl]phenyl]-4-[4-(4-tri-fluoromethylphenyl)thiazol-2-yl]benzenesulfonamide and pharmaceutically acceptable salts thereof.

  这项发明涉及用于治疗尿频、尿急和尿失禁的组合物，包括(R)-N-[4-[2-[[2-羟基-2-(吡啶-3-基)乙基]氨基]乙基]苯基]-4-[4-(4-三氟甲基苯基)噻唑-2-基]苯磺酰胺及其药学上可接受的盐。另一方面，这项发明涉及用于尿频、尿急和尿失禁的联合疗法，其中一种活性药物是(R)-N-[4-[2-[[2-羟基-2-(吡啶-3-基)乙基]氨基]乙基]苯基]-4-[4-(4-三氟甲基苯基)噻唑-2-基]苯磺酰胺及其药学上可接受的盐。
• Zwitterionic tachykinin receptor antagonists
  申请人：——

  公开号：US20020042431A1

  公开（公告）日：2002-04-11

  The present invention is directed to certain novel compounds represented by structural formula I: 1 or a pharmaceutically acceptable salt thereof, wherein R 3 , R 5 , R 6 , R 7 , R 8 , R 11 , R 12 R 13 , Q, W, X, Y and Z are defined herein. The invention is also concerned with pharmaceutical formulations comprising these novel compounds as active ingredients and the use of the novel compounds and their formulations in the treatment of certain disorders. The compounds of this invention are tachykinin receptor antagonists and are useful in the treatment of psychiatric disorders including depression and anxiety.

  本发明涉及由结构式I：1所代表的某些新化合物或其药用可接受的盐，其中R3、R5、R6、R7、R8、R11、R12、R13、Q、W、X、Y和Z在此定义。该发明还涉及含有这些新化合物作为活性成分的药物配方，以及该新化合物及其配方在治疗某些疾病中的用途。本发明的化合物是催吐肽受体拮抗剂，可用于治疗包括抑郁症和焦虑症在内的精神障碍。
• WO2007/146224
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2008/21029
  申请人：——

  公开号：——

  公开（公告）日：——