tert-butyl (3S,4S)-4-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-3-(o-tolyl)piperidine-1-carboxylate | 1076229-96-3

• 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: tert-butyl (3S,4S)-4-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-3-(o-tolyl)piperidine-1-carboxylate
• 英文别名: tert-butyl (3S,4S)-4-{[[3,5-bis(trifluoromethyl)benzyl](methyl)amino]carbonyl}-3-(2-methylphenyl)piperidine-1-carboxylate；tert-butyl (3S,4S)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-methylcarbamoyl]-3-(2-methylphenyl)piperidine-1-carboxylate
• CAS: 1076229-96-3
• 化学式: C₂₈H₃₂F₆N₂O₃
• 分子量: 558.564
• InChiKey: XLJJBLAIVOPVCC-XZOQPEGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl (3S,4S)-4-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-3-(o-tolyl)piperidine-1-carboxylate 在 盐酸 、 N-[(dimethylamino)-1H-1,2,3-triazolo[4,5-b]pyridine-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 (3S,4S)-N-(3,5-bis(trifluoromethyl)benzyl)-1-(1-(2-hydroxyacetyl)piperidine-4-carbonyl)-N-methyl-3-(o-tolyl)piperidine-4-carboxamide
  参考文献：
  名称：

  [EN] TRIPARTITE MODULATORS OF ENDOSOMAL G PROTEIN-COUPLED RECEPTORS
  [FR] MODULATEURS TRIPARTITES DE RÉCEPTEURS COUPLÉS AUX PROTÉINES G DES ENDOSOMES

  摘要：

  本发明涉及三部分化合物，包括用于内体高尔基蛋白偶联受体（如神经激肽-1受体）的调节子基团，一个连接物和一个适合将三部分化合物锚定到细胞膜的脂质锚。本发明还涉及一种前药和含有三部分化合物的药物组合物，以及利用三部分化合物治疗由内体高尔基蛋白偶联受体信号传导介导的疾病或紊乱的用途。

  公开号：

  WO2017112792A1
• 作为产物：
  描述：

  1-苄基-3-氧杂-4-哌啶甲酸乙酯 在 盐酸 、 四(三苯基膦)钯 、 sodium methylate 、 sodium hydride 、 potassium carbonate 、 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 甲醇 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 5.0~100.0 ℃ 、303.99 kPa 条件下， 反应 72.08h， 生成 tert-butyl (3S,4S)-4-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-3-(o-tolyl)piperidine-1-carboxylate
  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。
• 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。
• 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.
• [EN] TRIPARTITE MODULATORS OF ENDOSOMAL G PROTEIN-COUPLED RECEPTORS<br/>[FR] MODULATEURS TRIPARTITES DE RÉCEPTEURS COUPLÉS AUX PROTÉINES G DES ENDOSOMES
  申请人：TAKEDA PHARMACEUTICALS CO

  公开号：WO2017112792A1

  公开（公告）日：2017-06-29

  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.

  本发明涉及三部分化合物，包括用于内体高尔基蛋白偶联受体（如神经激肽-1受体）的调节子基团，一个连接物和一个适合将三部分化合物锚定到细胞膜的脂质锚。本发明还涉及一种前药和含有三部分化合物的药物组合物，以及利用三部分化合物治疗由内体高尔基蛋白偶联受体信号传导介导的疾病或紊乱的用途。
• 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.