2-(2-cyclohexyl-2-cyclopropylethyl)piperidine

• 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: 2-(2-cyclohexyl-2-cyclopropylethyl)piperidine
• 英文别名: 2-(2-Cyclohexyl-2-cyclopropylethyl)piperidine
• 化学式: C₁₆H₂₉N
• 分子量: 235.413
• InChiKey: PMTLFQLSDIJZBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  6-己内酯-2-酮 在 咪唑 、 copper(l) iodide 、 ammonium acetate 、 sodium cyanoborohydride 、 戴斯-马丁氧化剂 、 对甲苯磺酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 2-甲基四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 33.5h， 生成 2-(2-cyclohexyl-2-cyclopropylethyl)piperidine
  参考文献：
  名称：

  Development of Fluorinated Analogues of Perhexiline with Improved Pharmacokinetic Properties and Retained Efficacy

  摘要：

  We designed and synthesized perhexiline analogues that have the same therapeutic profile as the parent cardiovascular drug but lacking its metabolic liability associated with CYP2D6 metabolism. Cycloalkyl perhexiline analogues 6a-j were found to be unsuitable for further development, as they retained a pharmacokinetic profile very similar to that shown by the parent compound. Multistep synthesis of perhexiline analogues incorporating fluorine atoms onto the cyclohexyl ring(s) provided a range of different fluoroperhexiline analogues. Of these, analogues 50 (4,4-gem-difluoro) and 62 (4,4,4',4'-tetrafluoro) were highly stable and showed greatly reduced susceptibility to CYP2D6-mediated metabolism. In vitro efficacy studies demonstrated that a number of derivatives retained acceptable potency against CPT-1. Having the best balance of properties, 50 was selected for further evaluation. Like perhexiline, it was shown to be selectively concentrated in the myocardium and, using the Langendorff model, to be effective in improving both cardiac contractility and relaxation when challenged with high fat buffer.

  DOI：

  10.1021/acs.jmedchem.6b01592