(S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine | 939039-31-3

• 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: (S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine
• 英文别名: (1S)-1-(5-chloropyridin-2-yl)-1-[3-fluoro-5-(trifluoromethyl)phenyl]-2-phenylethanamine
• CAS: 939039-31-3
• 化学式: C₂₀H₁₅ClF₄N₂
• 分子量: 394.799
• InChiKey: QBFPQAHWHWSJHT-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  38.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine 在 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 (S)-1-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-cyclopentylurea
  参考文献：
  名称：

  Identification of a potent and metabolically stable series of fluorinated diphenylpyridylethanamine-based cholesteryl ester transfer protein inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2012.08.011
• 作为产物：
  描述：

  (5-chloropyridin-2-yl)(3-fluoro-5-(trifluoromethyl)phenyl)methanone 在 盐酸 、 titanium(IV) tetraethanolate 、 三氟化硼乙醚 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 甲基叔丁基醚 为溶剂， 反应 15.25h， 生成 (S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine
  参考文献：
  名称：

  叔羧胺的合成

  摘要：

  描述了使用一锅三组分反应有效合成叔卡宾胺，该反应采用中间亚胺盐的TMSC1活化，然后添加有机金属。随后以数克规模开发了利用Ellman亚磺胺的精选叔卡宾胺的优化第二代手性合成方法，并进行了描述。

  DOI：

  10.1016/j.tet.2012.01.050

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。
• Discovery of hydroxyl 1,2-diphenylethanamine analogs as potent cholesterol ester transfer protein inhibitors
  作者：Ji Jiang、Heather Finlay、James A. Johnson、Lalgudi Harikrishnan、Muthoni Kamau、Jennifer Qiao、Tammy Wang、Leonard Adam、David Taylor、Richard Yang、Paul Sleph、Alice Ye A. Chen、Xiaohong Yin、Ruth Wexler、Mark E. Salvati

  DOI：10.1016/j.bmcl.2016.05.058

  日期：2016.7

  analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. In an effort to improve the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series, polar groups were introduced to the N-linked quaternary center. Optimization of analogues for potency, in vitro liability profile and efficacy

  羟基1,2-二苯乙胺类似物被确定为胆固醇酯转移蛋白（CETP）的有效抑制剂，胆固醇酯转移蛋白是提高HDL胆固醇的治疗靶标。为了改善先前公开的二苯基吡啶乙乙胺（DPPE）系列中的药物性质，将极性基团引入到N-连接的季中心。优化效价，体外责任特征和功效的类似物导致鉴定了铅化合物16，该化合物在人CETP / apo-B100双转基因小鼠中显示出强大的药效学作用。
• Heterocyclic CETP inhibitors
  申请人：Bristol-Myers Squibb Company

  公开号：US07888376B2

  公开（公告）日：2011-02-15

  Compounds of formula Ia and Ib wherein A, B, C and R1 are described herein.

  化合物Ia和Ib的公式如下，其中A、B、C和R1的描述如下。
• WO2007/62342
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.