4-(4-carboxy-2-trifluoromethyl-phenyl)-piperidine-1-carboxylic acid benzyl ester | 1204331-78-1

• 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: 4-(4-carboxy-2-trifluoromethyl-phenyl)-piperidine-1-carboxylic acid benzyl ester
• 英文别名: 4-(1-phenylmethoxycarbonylpiperidin-4-yl)-3-(trifluoromethyl)benzoic acid
• CAS: 1204331-78-1
• 化学式: C₂₁H₂₀F₃NO₄
• 分子量: 407.389
• InChiKey: KUMDVMBVJGABAA-UHFFFAOYSA-N

物化性质

• 沸点：
  522.0±50.0 °C(Predicted)
• 密度：
  1.331±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(4-carboxy-2-trifluoromethyl-phenyl)-piperidine-1-carboxylic acid benzyl ester 在 palladium hydroxide, 20 wt% on carbon 2-氯-1-甲基吡啶碘化物 、 氢气 作用下， 以 N-甲基吡咯烷酮 、 乙醇 为溶剂， 反应 19.5h， 生成 N-(4-piperidin-4-yl-3-trifluoromethylbenzoyl)-N'-(tert-butoxycarbonyl)guanidine
  参考文献：
  名称：

  [EN] PYRROLIDINYL AND PIPERIDINYL COMPOUNDS USEFUL AS NHE-1 INHIBITORS
  [FR] COMPOSÉS PYRROLIDINYLIQUE ET PIPÉRIDINYLIQUE UTILES COMME INHIBITEURS DE NHE-1

  摘要：

  公开了公式（I）的化合物和本发明的组合物，它们是钠质子交换器同型-1（NHE-1）的抑制剂。还公开了使用和制造相同的方法。

  公开号：

  WO2010005783A1
• 作为产物：
  描述：

  4-piperidin-4-yl-3-trifluoromethyl-benzoic acid methyl ester hydrochloride 在 potassium carbonate 、 二异丙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 21.0h， 生成 4-(4-carboxy-2-trifluoromethyl-phenyl)-piperidine-1-carboxylic acid benzyl ester
  参考文献：
  名称：

  Identification of a Potent Sodium Hydrogen Exchanger Isoform 1 (NHE1) Inhibitor with a Suitable Profile for Chronic Dosing and Demonstrated Cardioprotective Effects in a Preclinical Model of Myocardial Infarction in the Rat

  摘要：

  Sodium-hydrogen exchanger isoform 1 (NHE1) is a ubiquitously expressed transmembrane ion channel responsible for intracellular pH regulation. During myocardial ischemia, low pH activates NHE1 and causes increased intracellular calcium levels and aberrant cellular processes, leading to myocardial stunning, arrhythmias, and ultimately cell damage and death. The role of NHE1 in cardiac injury has prompted interest in the development of NHE1 inhibitors for the treatment of heart failure. This report outlines our efforts to identify a compound suitable for once daily, oral administration with low drug-drug interaction potential starting from NHE1 inhibitor sabiporide. Substitution of a piperidine for the piperazine of sabiporide followed by replacement of the pyrrole moiety and subsequent optimization to improve potency and eliminate off-target activities resulted in the identification of N-[4-(1-acetyl-piperidin-4-yl)-3-trifluoromethyl-benzoyl]-guanidine (60). Pharmacological evaluation of 60 revealed a remarkable ability to prevent ischemic damage in an ex vivo model of ischemia reperfusion injury in isolated rat hearts.

  DOI：

  10.1021/jm300601d

文献信息

• Pyrrolidinyl and Piperidinyl Compounds Useful as NHE-1 Inhibitiors
  申请人：Bentzien Joerg Martin

  公开号：US20110118262A1

  公开（公告）日：2011-05-19

  Disclosed are compounds of formula (I) and compositions of the present invention which are inhibitors of the sodium proton exchanger isoform-1 (NHE-I). Also disclosed are methods of using and making the same.

  本发明揭示了化合物(I)和组合物，它们是钠质子交换器亚型-1（NHE-I）的抑制剂。同时还揭示了使用和制备这些化合物的方法。
• PYRROLIDINYL AND PIPERIDINYL COMPOUNDS USEFUL AS NHE-1 INHIBITORS
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2321274A1

  公开（公告）日：2011-05-18