1-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-cyclopentylurea | 939415-92-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 1-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-cyclopentylurea
• 英文别名: 1-Cyclopentyl-3-[alpha-(5-chloro-2-pyridinyl)-alpha-benzyl-3-fluoro-5-(trifluoromethyl)benzyl]urea；1-[1-(5-chloropyridin-2-yl)-1-[3-fluoro-5-(trifluoromethyl)phenyl]-2-phenylethyl]-3-cyclopentylurea
• CAS: 939415-92-6
• 化学式: C₂₆H₂₄ClF₄N₃O
• 分子量: 505.943
• InChiKey: BLGKGVMDNWKDHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  54
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-甲基环己胺 、 1-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-cyclopentylurea 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 0.42h， 以88%的产率得到3-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-1-cyclohexyl-1-methylurea
  参考文献：
  名称：

  微波辅助尿素转氨基

  摘要：

  描述了由环戊基或异丙基取代的脲有效形成微波辅助的脲。通过在THF / DMSO中在150°C下用过量（5-10当量）胺进行微波辐射，通过微波辐照环戊基或异丙基取代的脲，这种新颖的转酰胺方法可以提供高收率的脲IIa – IIq。

  DOI：

  10.1016/j.tetlet.2016.02.103
• 作为产物：
  描述：

  1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine 、 环戊基异氰酸酯 以 1,4-二氧六环 为溶剂， 反应 18.0h， 以40%的产率得到1-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-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

文献信息

• HETEROCYCLIC CETP INHIBITORS
  申请人：Salvati E. Mark

  公开号：US20070161685A1

  公开（公告）日：2007-07-12

  Compounds of formula Ia and Ib wherein A, B, C and R 1 are described herein.

  式Ia和Ib的化合物 其中A、B、C和R1 如本文所述。
• US7888376B2
  申请人：——

  公开号：US7888376B2

  公开（公告）日：2011-02-15
• [EN] HETEROCYCLIC CETP INHIBITORS<br/>[FR] INHIBITEURS DE CETP HETEROCYCLIQUES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2007062314A2

  公开（公告）日：2007-05-31

  [EN] Compounds of formula Ia and Ib wherein A, B, C and R₁ are described herein.
  [FR] La présente invention concerne des composés de formules Ia et Ib dans lesquelles A, B, C et R₁ ont les correspondances indiquées dans l'invention.
• Diphenylpyridylethanamine (DPPE) Derivatives as Cholesteryl Ester Transfer Protein (CETP) Inhibitors
  作者：Lalgudi S. Harikrishnan、Heather J. Finlay、Jennifer X. Qiao、Muthoni G. Kamau、Ji Jiang、Tammy C. Wang、James Li、Christopher B. Cooper、Michael A. Poss、Leonard P. Adam、David S. Taylor、Alice Ye A. Chen、Xiaohong Yin、Paul G. Sleph、Richard Z. Yang、Doree F. Sitkoff、Michael A. Galella、David S. Nirschl、Katy Van Kirk、Arthur V. Miller、Christine S. Huang、Ming Chang、Xue-Qing Chen、Mark E. Salvati、Ruth R. Wexler、R. Michael Lawrence

  DOI：10.1021/jm300611v

  日期：2012.7.12

  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.
• Microwave-assisted transamidation of ureas
  作者：Tammy C. Wang、Jennifer X. Qiao

  DOI：10.1016/j.tetlet.2016.02.103

  日期：2016.5

  An effective microwave-assisted urea formation from cyclopentyl- or isopropyl-substituted ureas is described. This novel transamidation methodology provided ureas IIa–IIq in good yields via microwave irradiation of the cyclopentyl- or isopropyl-substituted ureas with excess (5–10 equiv) of amines at 150 °C in THF/DMSO.

  描述了由环戊基或异丙基取代的脲有效形成微波辅助的脲。通过在THF / DMSO中在150°C下用过量（5-10当量）胺进行微波辐射，通过微波辐照环戊基或异丙基取代的脲，这种新颖的转酰胺方法可以提供高收率的脲IIa – IIq。