ethyl 3-(4-((1R,2R)-2-(2-(4-(trifluoromethyl)phenyl)pyrimidin-5-yl)cyclopentyl)benzamido)propanoate | 1592735-42-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 3-(4-((1R,2R)-2-(2-(4-(trifluoromethyl)phenyl)pyrimidin-5-yl)cyclopentyl)benzamido)propanoate
• CAS: 1592735-42-6
• 化学式: C₂₈H₂₈F₃N₃O₃
• 分子量: 511.544
• InChiKey: ITUKRLXAEGZJHI-ZEQRLZLVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  37.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  81.18
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ethyl 3-(4-((1R,2R)-2-(2-(4-(trifluoromethyl)phenyl)pyrimidin-5-yl)cyclopentyl)benzamido)propanoate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 18.0h， 以91%的产率得到3-[[4-[(1R,2R)-2-[2-[4-(trifluoromethyl)phenyl]pyrimidin-5-yl]cyclopentyl]benzoyl]amino]propanoic acid
  参考文献：
  名称：

  Identification of a novel conformationally constrained glucagon receptor antagonist

  摘要：

  Identification of orally active, small molecule antagonists of the glucagon receptor represents a novel treatment paradigm for the management of type 2 diabetes mellitus. The present work discloses novel glucagon receptor antagonists, identified via conformational constraint of current existing literature antagonists. Optimization of lipophilic ligand efficiency (LLE or LipE) culminated in enantiomers (+)-trans-26 and (-)-trans-27 which exhibit good physicochemical and in vitro drug metabolism profiles. In vivo, significant pharmacokinetic differences were noted with the two enantiomers, which were primarily driven through differences in clearance rates. Enantioselective oxidation by cytochrome P450 was ruled out as a causative factor for pharmacokinetic differences. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.090
• 作为产物：
  描述：

  在 N-羟基-7-氮杂苯并三氮唑 、 1,2-二氯乙烷 、 三乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 生成 ethyl 3-(4-((1R,2R)-2-(2-(4-(trifluoromethyl)phenyl)pyrimidin-5-yl)cyclopentyl)benzamido)propanoate
  参考文献：
  名称：

  Identification of a novel conformationally constrained glucagon receptor antagonist

  摘要：

  Identification of orally active, small molecule antagonists of the glucagon receptor represents a novel treatment paradigm for the management of type 2 diabetes mellitus. The present work discloses novel glucagon receptor antagonists, identified via conformational constraint of current existing literature antagonists. Optimization of lipophilic ligand efficiency (LLE or LipE) culminated in enantiomers (+)-trans-26 and (-)-trans-27 which exhibit good physicochemical and in vitro drug metabolism profiles. In vivo, significant pharmacokinetic differences were noted with the two enantiomers, which were primarily driven through differences in clearance rates. Enantioselective oxidation by cytochrome P450 was ruled out as a causative factor for pharmacokinetic differences. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.090