(3S,4S)-4-{N-1-(S)-(3,5-bistrifluoromethylphenyl)ethyl-N-methyl}aminocarbonyl-3-(4-fluoro-2-methylphenyl)piperidine | 873457-53-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3S,4S)-4-{N-1-(S)-(3,5-bistrifluoromethylphenyl)ethyl-N-methyl}aminocarbonyl-3-(4-fluoro-2-methylphenyl)piperidine
• 英文别名: (3S,4S)-N-[(1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]-3-(4-fluoro-2-methylphenyl)-N-methylpiperidine-4-carboxamide
• CAS: 873457-53-5
• 化学式: C₂₄H₂₅F₇N₂O
• 分子量: 490.464
• InChiKey: CQDXTGUIERXTNR-SZFUDVHCSA-N

物化性质

• 沸点：
  483.6±45.0 °C(Predicted)
• 密度：
  1.266±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (3S,4S)-4-{N-1-(S)-(3,5-bistrifluoromethylphenyl)ethyl-N-methyl}aminocarbonyl-3-(4-fluoro-2-methylphenyl)piperidine 、 草氨酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 (3S,4S)-1-[amino(oxo)acetyl]-N-((1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl)-3-(4-fluoro-2-methylphenyl)-N-methylpiperidine-4-carboxamide
  参考文献：
  名称：

  Novel 3-phenylpiperidine-4-carboxamides as highly potent and orally long-acting neurokinin-1 receptor antagonists with reduced CYP3A induction

  摘要：

  The synthesis and biological evaluation of a series of novel 3-phenylpiperidine-4-carboxamide derivatives are described. These compounds are generated by hybridization of the substructures from two types of tachykinin NK1 receptor antagonists. Compound 42 showed high metabolic stability and excellent efficacy in the guinea-pig GR-73637-induced locomotive activity assay at 1 and 24 h after oral administration. It also exhibited good pharmacokinetic profiles in four animal species, and a low potential in a pregnane X receptor induction assay. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.048
• 作为产物：
  描述：

  1-甲基-1,2,3,6-四氢吡啶-4-羧酸乙酯 在 盐酸 、 copper(l) iodide 、 草酰氯 、 1-氯乙基氯甲酸酯 、 sodium methylate 、 柠檬酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 水 、 乙酸乙酯 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 28.0h， 生成 (3S,4S)-4-{N-1-(S)-(3,5-bistrifluoromethylphenyl)ethyl-N-methyl}aminocarbonyl-3-(4-fluoro-2-methylphenyl)piperidine
  参考文献：
  名称：

  Novel 3-phenylpiperidine-4-carboxamides as highly potent and orally long-acting neurokinin-1 receptor antagonists with reduced CYP3A induction

  摘要：

  The synthesis and biological evaluation of a series of novel 3-phenylpiperidine-4-carboxamide derivatives are described. These compounds are generated by hybridization of the substructures from two types of tachykinin NK1 receptor antagonists. Compound 42 showed high metabolic stability and excellent efficacy in the guinea-pig GR-73637-induced locomotive activity assay at 1 and 24 h after oral administration. It also exhibited good pharmacokinetic profiles in four animal species, and a low potential in a pregnane X receptor induction assay. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.048

文献信息

• [EN] PIPERIDINE COMPOUND AND PROCESS FOR PREPARING THE SAME<br/>[FR] COMPOSÉ DE PIPÉRIDINE ET PROCÉDÉ DE PRÉPARATION DE CE COMPOSÉ
  申请人：TANABE SEIYAKU CO

  公开号：WO2006004195A1

  公开（公告）日：2006-01-12

  The present invention is to provide a piperidine compound represented by the formula [I]: wherein Ring A is an optionally substituted benzene ring, Ring B is an optionally substituted benzene ring, R1 is hydrogen atom or a substituent for amino group, R2 is hydrogen atom, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted alkyl group, a substituted carbonyl group or a halogen atom, Z is oxygen atom or -N (R3)-, R3 is hydrogen atom or an optionally substituted alkyl group, R4a and R4b may be the same or different, and each is hydrogen atom or an optionally substituted alkyl group, or may be bonded to each other at the both ends to form an alkylene group, or a pharmaceutically acceptable salt thereof, which has an excellent tachykinin receptor antagonistic action.

  本发明提供的是一种由式[I]表示的哌啶化合物，其中环A是一个可选择取代的苯环，环B是一个可选择取代的苯环，R1是氢原子或氨基的取代基，R2是氢原子、一个可选择取代的羟基、一个可选择取代的氨基、一个可选择取代的烷基、一个取代的羰基或卤原子，Z是氧原子或-N(R3)-，R3是氢原子或一个可选择取代的烷基，R4a和R4b可以相同也可以不同，每个都是氢原子或一个可选择取代的烷基，或者可以在两端结合在一起形成一个烷基链，或其药学上可接受的盐，具有优异的催吐肽受体拮抗作用。
• NK1 receptor antagonist
  申请人：KISSEI PHARMACEUTICAL CO., LTD.

  公开号：US10399949B2

  公开（公告）日：2019-09-03

  A problem of the present invention is to provide a new compound which has NK1 receptor antagonist activity, and thus is useful for the prevention or treatment of cancer-chemotherapy-induced nausea and vomiting. A compound represented by the formula (I): wherein W represents a fluorine atom and the like, ring A represents a cycloalkyl and the like, X1 represents CH or N, R represents methyl and the like, Y represents 0 to 2, U1, U2 and U3 each independently represents a single bond and the like, or a pharmaceutically acceptable salt thereof. The compounds of the present invention or pharmaceutically acceptable salts thereof have an excellent NK1 receptor antagonist activity, and thus are also useful as an agent for the prevention or treatment of cancer-chemotherapy-induced nausea and vomiting.

  本发明的一个问题是提供一种新化合物，它具有 NK1 受体拮抗剂活性，因此可用于预防或治疗癌症化疗引起的恶心和呕吐。 一种由式（I）代表的化合物： 其中 W 代表氟原子等，环 A 代表环烷基等，X1 代表 CH 或 N，R 代表甲基等，Y 代表 0 至 2，U1、U2 和 U3 各自独立地代表单键等，或其药学上可接受的盐。本发明的化合物或其药学上可接受的盐具有优异的 NK1 受体拮抗剂活性，因此也可用作预防或治疗癌症化疗引起的恶心和呕吐的药物。
• Tripartite modulators of endosomal G protein-coupled receptors
  申请人：Endosome Therapeutics, Inc.

  公开号：US11324832B2

  公开（公告）日：2022-05-10

  The present invention relates to tripartite compounds comprising a modulator moiety for endosomal G protein-coupled receptors like neurokinin-1 receptor, a linker and a lipid anchor suitable for anchoring the tripartite compound into a plasma membrane. The present invention also relates to a prodrug and a pharmaceutical composition comprising the tripartite compound and the use of the tripartite compound for the treatment of a disease or disorder mediated by endosomal G protein-coupled receptors signalling like NK1R signalling.

  本发明涉及三方化合物，其包含神经激肽-1 受体等内泌体 G 蛋白偶联受体的调节剂分子、连接体和适于将三方化合物锚定到质膜上的脂质锚。本发明还涉及包含三方化合物的原药和药物组合物，以及三方化合物用于治疗由内体G蛋白偶联受体信号（如NK1R信号）介导的疾病或紊乱。
• NK1 RECEPTOR ANTAGONIST
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：EP3388423B1

  公开（公告）日：2020-05-27
• TRIPARTITE MODULATORS OF ENDOSOMAL G PROTEIN-COUPLED RECEPTORS
  申请人：Bunnett Nigel W.

  公开号：US20190000981A1

  公开（公告）日：2019-01-03

  The present invention relates to tripartite compounds comprising a modulator moiety for endosomal G protein-coupled receptors like neurokinin-1 receptor, a linker and a lipid anchor suitable for anchoring the tripartite compound into a plasma membrane. The present invention also relates to a prodrug and a pharmaceutical composition comprising the tripartite compound and the use of the tripartite compound for the treatment of a disease or disorder mediated by endosomal G protein-coupled receptors signalling like NK 1 R signalling.