(S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-(5-methyl-1,2,4-oxadiazol-3-yl)ethan-1-amine | 1383788-00-8

• 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: (S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-(5-methyl-1,2,4-oxadiazol-3-yl)ethan-1-amine
• CAS: 1383788-00-8
• 化学式: C₁₇H₁₃ClF₄N₄O
• 分子量: 400.763
• InChiKey: QKYFMZNGTFBOHF-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.03
• 重原子数：
  27.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  77.83
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  环戊基异氰酸酯 、 (S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-(5-methyl-1,2,4-oxadiazol-3-yl)ethan-1-amine 在 盐酸 、 柠檬酸 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 以43%的产率得到(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-(5-methyl-1,2,4-oxadiazol-3-yl)ethyl)-3-cyclopentylurea
  参考文献：
  名称：

  Diphenylpyridylethanamine (DPPE) Derivatives as Cholesteryl Ester Transfer Protein (CETP) Inhibitors

  摘要：

  A series of diphenylpyridylethanamine (DPPE) derivatives was identified exhibiting potent CETP inhibition. Replacing the labile ester functionality in the initial lead 7 generated a series of amides and ureas. Further optimization of the DPPE series for potency resulted in the discovery of cyclopentylurea 15d, which demonstrated a reduction in cholesterol ester transfer activity (48% of predose level) in hCETP/apoB-100 dual transgenic mice. The PK profile of 15d was suboptimal, and further optimization of the N-terminus resulted in the discovery of amide 20 with an improved PK profile and robust efficacy in transgenic hCETP/apoB-100 mice and in hamsters. Compound 20 demonstrated no significant changes in either mean arterial blood pressure or heart rate in telemeterized rats despite sustained high exposures.

  DOI：

  10.1021/jm300611v
• 作为产物：
  描述：

  (S)-N-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-(5-methyl-1,2,4-oxadiazol-3-yl)ethyl)-2-methylpropane-2-sulfinamide 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 以100%的产率得到(S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-(5-methyl-1,2,4-oxadiazol-3-yl)ethan-1-amine
  参考文献：
  名称：

  Diphenylpyridylethanamine (DPPE) Derivatives as Cholesteryl Ester Transfer Protein (CETP) Inhibitors

  摘要：

  A series of diphenylpyridylethanamine (DPPE) derivatives was identified exhibiting potent CETP inhibition. Replacing the labile ester functionality in the initial lead 7 generated a series of amides and ureas. Further optimization of the DPPE series for potency resulted in the discovery of cyclopentylurea 15d, which demonstrated a reduction in cholesterol ester transfer activity (48% of predose level) in hCETP/apoB-100 dual transgenic mice. The PK profile of 15d was suboptimal, and further optimization of the N-terminus resulted in the discovery of amide 20 with an improved PK profile and robust efficacy in transgenic hCETP/apoB-100 mice and in hamsters. Compound 20 demonstrated no significant changes in either mean arterial blood pressure or heart rate in telemeterized rats despite sustained high exposures.

  DOI：

  10.1021/jm300611v