methyl (3R)-3-[4-[[3-[4-(trifluoromethyl)phenyl]phenyl]methoxy]phenyl]hex-4-enoate

• 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: methyl (3R)-3-[4-[[3-[4-(trifluoromethyl)phenyl]phenyl]methoxy]phenyl]hex-4-enoate
• 化学式: C₂₇H₂₅F₃O₃
• 分子量: 454.489
• InChiKey: BBTQMBDSQVVZTE-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (3R)-3-[4-[[3-[4-(trifluoromethyl)phenyl]phenyl]methoxy]phenyl]hex-4-enoate 在 2,6-二甲基吡啶 、 sodium chlorite 、 potassium dihydrogenphosphate 、 四氧化锇 、 5%-palladium/activated carbon 、 氨 、 氢气 、 双氧水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 丙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 乙腈 、 叔丁醇 为溶剂， 反应 20.33h， 生成 (S)-methyl 3-(4-hydroxyphenyl)-3-(2-methyl-2H-1,2,4-triazol-3-yl)propanoate
  参考文献：
  名称：

  Optimization of GPR40 Agonists for Type 2 Diabetes

  摘要：

  GPR40 (FFA1 and FFAR1) has gained significant interest as a target for the treatment of type 2 diabetes. TAK-875 (1), a GPR40 agonist, lowered hemoglobin A1c (HbA1c) and lowered both postprandial and fasting blood glucose levels in type 2 diabetic patients in phase II clinical trials. We optimized phenylpropanoic acid derivatives as GPR40 agonists and identified AMG 837 (2) as a clinical candidate. Here we report our efforts in searching for structurally distinct back-ups for AMG 837. These efforts led to the identification of more polar GPR40 agonists, such as AM-4668 (10), that have improved potency, excellent pharmacokinetic properties across species, and minimum central nervous system (CNS) penetration.

  DOI：

  10.1021/ml400501x
• 作为产物：
  描述：

  (3S)-3-[4-(4'-trifluoromethyl-biphenyl-3-ylmethoxy)-phenyl]-hex-4-ynoic acid methyl ester 在 喹啉 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 8.0h， 以92%的产率得到methyl (3R)-3-[4-[[3-[4-(trifluoromethyl)phenyl]phenyl]methoxy]phenyl]hex-4-enoate
  参考文献：
  名称：

  Optimization of GPR40 Agonists for Type 2 Diabetes

  摘要：

  GPR40 (FFA1 and FFAR1) has gained significant interest as a target for the treatment of type 2 diabetes. TAK-875 (1), a GPR40 agonist, lowered hemoglobin A1c (HbA1c) and lowered both postprandial and fasting blood glucose levels in type 2 diabetic patients in phase II clinical trials. We optimized phenylpropanoic acid derivatives as GPR40 agonists and identified AMG 837 (2) as a clinical candidate. Here we report our efforts in searching for structurally distinct back-ups for AMG 837. These efforts led to the identification of more polar GPR40 agonists, such as AM-4668 (10), that have improved potency, excellent pharmacokinetic properties across species, and minimum central nervous system (CNS) penetration.

  DOI：

  10.1021/ml400501x