1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenyl-1-(4-(trifluoromethyl)pyridin-2-yl)ethanamine | 939426-21-8

• 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-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenyl-1-(4-(trifluoromethyl)pyridin-2-yl)ethanamine
• 英文别名: 1-[3-fluoro-5-(trifluoromethyl)phenyl]-2-phenyl-1-[4-(trifluoromethyl)pyridin-2-yl]ethanamine
• CAS: 939426-21-8
• 化学式: C₂₁H₁₅F₇N₂
• 分子量: 428.352
• InChiKey: DXJMSWJRDXWYSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  38.9
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenyl-1-(4-(trifluoromethyl)pyridin-2-yl)ethanamine 、 环戊基异氰酸酯 以 1,4-二氧六环 为溶剂， 反应 16.0h， 生成 3-cyclopentyl-1-[(1S)-1-[3-fluoro-5-(trifluoromethyl)phenyl]-2-phenyl-1-[4-(trifluoromethyl)pyridin-2-yl]ethyl]urea
  参考文献：
  名称：

  Triphenylethanamine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors: Discovery of N-[(1R)-1-(3-Cyclopropoxy-4-fluorophenyl)-1-[3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl]-2-phenylethyl]-4-fluoro-3-(trifluoromethyl)benzamide (BMS-795311)

  摘要：

  Cholesteryl ester transfer protein (CETP) inhibitors raise HDL-C in animals and humans and may be antiatherosclerotic by enhancing reverse cholesterol transport (RCT). In this article, we describe the lead optimization efforts resulting in the discovery of a series of triphenylethanamine (TPE) ureas and amides as potent and orally available CETP inhibitors. Compound 10g is a potent CETP inhibitor that maximally inhibited cholesteryl ester (CE) transfer activity at an oral dose of 1 mg/kg in human CETP/apoB-100 dual transgenic mice and increased HDL cholesterol content and size comparable to torcetrapib (1) in moderately-fat fed hamsters. In contrast to the off-target liabilities with 1, no blood pressure increase was observed with 10g in rat telemetry studies and no increase of aldosterone synthase (CYP11B2) was detected in H295R cells. On the basis of its preclinical profile, compound 10g was advanced into preclinical safety studies.

  DOI：

  10.1021/acs.jmedchem.5b01363
• 作为产物：
  描述：

  3-氟-5-(三氟甲基)苯甲腈 、 2-溴-4-(三氟甲基)吡啶 在 正丁基锂 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 为溶剂， 反应 16.17h， 生成 1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenyl-1-(4-(trifluoromethyl)pyridin-2-yl)ethanamine
  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。
• 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。
• 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.
• Triphenylethanamine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors: Discovery of <i>N</i>-[(1<i>R</i>)-1-(3-Cyclopropoxy-4-fluorophenyl)-1-[3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl]-2-phenylethyl]-4-fluoro-3-(trifluoromethyl)benzamide (BMS-795311)
  作者：Jennifer X. Qiao、Tammy C. Wang、Leonard P. Adam、Alice Ye A. Chen、David S. Taylor、Richard Z. Yang、Shaobin Zhuang、Paul G. Sleph、Julia P. Li、Danshi Li、Xiaohong Yin、Ming Chang、Xue-Qing Chen、Hong Shen、Jianqing Li、Daniel Smith、Dauh-Rurng Wu、Leslie Leith、Lalgudi S. Harikrishnan、Muthoni G. Kamau、Michael M. Miller、Donna Bilder、Richard Rampulla、Yi-Xin Li、Carrie Xu、R. Michael Lawrence、Michael A. Poss、Paul Levesque、David A. Gordon、Christine S. Huang、Heather J. Finlay、Ruth R. Wexler、Mark E. Salvati

  DOI：10.1021/acs.jmedchem.5b01363

  日期：2015.11.25

  Cholesteryl ester transfer protein (CETP) inhibitors raise HDL-C in animals and humans and may be antiatherosclerotic by enhancing reverse cholesterol transport (RCT). In this article, we describe the lead optimization efforts resulting in the discovery of a series of triphenylethanamine (TPE) ureas and amides as potent and orally available CETP inhibitors. Compound 10g is a potent CETP inhibitor that maximally inhibited cholesteryl ester (CE) transfer activity at an oral dose of 1 mg/kg in human CETP/apoB-100 dual transgenic mice and increased HDL cholesterol content and size comparable to torcetrapib (1) in moderately-fat fed hamsters. In contrast to the off-target liabilities with 1, no blood pressure increase was observed with 10g in rat telemetry studies and no increase of aldosterone synthase (CYP11B2) was detected in H295R cells. On the basis of its preclinical profile, compound 10g was advanced into preclinical safety studies.