(3S,4S)-1-[amino(oxo)acetyl]-N-((1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl)-3-(4-fluoro-2-methylphenyl)-N-methylpiperidine-4-carboxamide | 1076228-22-2

• 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)-1-[amino(oxo)acetyl]-N-((1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl)-3-(4-fluoro-2-methylphenyl)-N-methylpiperidine-4-carboxamide
• 英文别名: (3S,4S)-1-[amino(oxo)acetyl]-N-{(1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-3-(4-fluoro-2-methylphenyl)-N-methylpiperidine-4-carboxamide；(3S,4S)-N-[(1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]-3-(4-fluoro-2-methylphenyl)-N-methyl-1-oxamoylpiperidine-4-carboxamide
• CAS: 1076228-22-2
• 化学式: C₂₆H₂₆F₇N₃O₃
• 分子量: 561.5
• InChiKey: SRLYUYRWDOPUDB-SZFUDVHCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  39
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  83.7
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 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 、 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 、 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 42.0h， 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

文献信息

• Piperidine derivative and use thereof
  申请人：Shirai Junya

  公开号：US20080275085A1

  公开（公告）日：2008-11-06

  The present invention provides a novel piperidine derivative and a tachykinin receptor antagonist containing same, as well as a compound represented by the formula: wherein R 1 is carbamoylmethyl, methylsulfonylethylcarbonyl and the like; R 2 is methyl or cyclopropyl; R 3 is a hydrogen atom or methyl; R 4 is a chlorine atom or trifluoromethyl; R 5 is a chlorine atom or trifluoromethyl; and a group represented by the formula: is a group represented by the formula: wherein R 6 is a hydrogen atom, methyl, ethyl or isopropyl; R 7 is a hydrogen atom, methyl or a chlorine atom; and R 8 is a hydrogen atom, a fluorine atom, a chlorine atom or methyl; or 3-methylthiophen-2-yl, and a salt thereof.

  本发明提供了一种新颖的哌啶衍生物和含有该衍生物的催吐肽受体拮抗剂，以及由下式表示的化合物： 其中R1为羰胺甲基、甲磺酰乙基羰基等；R2为甲基或环丙基；R3为氢原子或甲基；R4为氯原子或三氟甲基；R5为氯原子或三氟甲基；以及由下式表示的基团： 是由下式表示的基团： 其中R6为氢原子、甲基、乙基或异丙基；R7为氢原子、甲基或氯原子；R8为氢原子、氟原子、氯原子或甲基；或3-甲基噻吩-2-基，并且其盐。
• Novel 3-phenylpiperidine-4-carboxamides as highly potent and orally long-acting neurokinin-1 receptor antagonists with reduced CYP3A induction
  作者：Junya Shirai、Hideyuki Sugiyama、Shinji Morimoto、Hironobu Maezaki、Yasuharu Yamamoto、Satoshi Okanishi、Izumi Kamo、Shiho Matsumoto、Keiko Ishigami、Nobuhiro Inatomi、Akio Imanishi、Makiko Kawamoto、Naoki Tarui、Tadatoshi Hashimoto、Yoshinori Ikeura

  DOI：10.1016/j.bmc.2011.11.048

  日期：2012.1

  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.