(3RS,4RS)-N4-[3,5-bis(trifluoromethyl)benzyl]-3-(4-fluoro-2-methylphenyl)-N1-methylpiperidine-1,4-dicarboxamide

• 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: (3RS,4RS)-N4-[3,5-bis(trifluoromethyl)benzyl]-3-(4-fluoro-2-methylphenyl)-N1-methylpiperidine-1,4-dicarboxamide
• 英文别名: (3S,4S)-4-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-3-(4-fluoro-2-methylphenyl)-4-N-methylpiperidine-1,4-dicarboxamide
• 化学式: C₂₄H₂₄F₇N₃O₂
• 分子量: 519.462
• InChiKey: ALFJIXABJRNKLR-VQTJNVASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  36
• 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：
  66.6
• 氢给体数：
  1
• 氢受体数：
  9

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 、 1-氯乙基氯甲酸酯 、 水 、 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 、 potassium hydroxide 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 水 、 乙酸乙酯 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.0h， 生成 (3RS,4RS)-N4-[3,5-bis(trifluoromethyl)benzyl]-3-(4-fluoro-2-methylphenyl)-N1-methylpiperidine-1,4-dicarboxamide
  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

• 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.