(R)-1-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-cyclopentylurea | 939415-97-1

• 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: (R)-1-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-cyclopentylurea
• 英文别名: 1-[(1R)-1-(5-chloropyridin-2-yl)-1-[3-fluoro-5-(trifluoromethyl)phenyl]-2-phenylethyl]-3-cyclopentylurea
• CAS: 939415-97-1
• 化学式: C₂₆H₂₄ClF₄N₃O
• 分子量: 505.943
• InChiKey: BLGKGVMDNWKDHK-RUZDIDTESA-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

• 作为产物：
  描述：

  1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine 在 chiral SFC 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 20.0~35.0 ℃ 、10.0 MPa 条件下， 反应 18.0h， 生成 (R)-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。
• Identification of a potent and metabolically stable series of fluorinated diphenylpyridylethanamine-based cholesteryl ester transfer protein inhibitors
  作者：Michael M. Miller、Yalei Liu、Ji Jiang、James A. Johnson、Muthoni Kamau、David S. Nirschl、Yufeng Wang、Lalgudi Harikrishnan、David S. Taylor、Alice Ye A. Chen、Xiaohong Yin、Ramakrishna Seethala、Tara L. Peterson、Tatyana Zvyaga、Jun Zhang、Christine S. Huang、Ruth R. Wexler、Michael A. Poss、R. Michael Lawrence、Leonard P. Adam、Mark E. Salvati

  DOI：10.1016/j.bmcl.2012.08.011

  日期：2012.10

  A novel series of diphenylpyridylethanamine-based inhibitors of cholesteryl ester transfer protein is described. Optimization of the urea moiety, particularly by incorporation of fluorine, is explored to balance in vitro metabolic stability with CETP potency in the whole plasma assay. (c) 2012 Elsevier Ltd. All rights reserved.
• US7888376B2
  申请人：——

  公开号：US7888376B2

  公开（公告）日：2011-02-15