(3S)-3-(5-chloropyridin-2-yl)-3-(cyclopentylcarbamoylamino)-3-[3-fluoro-5-(trifluoromethyl)phenyl]propanamide | 1383788-01-9

• 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: (3S)-3-(5-chloropyridin-2-yl)-3-(cyclopentylcarbamoylamino)-3-[3-fluoro-5-(trifluoromethyl)phenyl]propanamide
• CAS: 1383788-01-9
• 化学式: C₂₁H₂₁ClF₄N₄O₂
• 分子量: 472.87
• InChiKey: CFXBACVJFBXADE-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  97.1
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3S)-3-(5-chloropyridin-2-yl)-3-(cyclopentylcarbamoylamino)-3-[3-fluoro-5-(trifluoromethyl)phenyl]propanamide 、 N,N-二甲基甲酰胺 在 一水合肼 、 溶剂黄146 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 1.5h， 以2.1 mg的产率得到(S)-1-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-(1H-1,2,4-triazol-5-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)-2-cyano-1-(3-fluoro-5-(trifluoromethyl)phenyl)ethyl)-2-methylpropane-2-sulfinamide 在 盐酸 、 柠檬酸 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 1,2-二氯乙烷 为溶剂， 生成 (3S)-3-(5-chloropyridin-2-yl)-3-(cyclopentylcarbamoylamino)-3-[3-fluoro-5-(trifluoromethyl)phenyl]propanamide
  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