4-(pyridin-2-yl)-3-(trifluoromethyl)benzenamine | 1324003-76-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-(pyridin-2-yl)-3-(trifluoromethyl)benzenamine
• 英文别名: 4-(pyridin-2-yl)-3-(trifluoromethyl)aniline；4-Pyridin-2-yl-3-(trifluoromethyl)aniline
• CAS: 1324003-76-0
• 化学式: C₁₂H₉F₃N₂
• 分子量: 238.212
• InChiKey: CWOADSITESTXAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  38.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(pyridin-2-yl)-3-(trifluoromethyl)benzenamine 、 2-methoxybenzoyl isocyanate 以 乙腈 为溶剂， 反应 1.5h， 以46%的产率得到2-methoxy-N-((4-(pyridin-2-yl)-3-(trifluoromethyl)phenyl)carbamoyl)benzamide
  参考文献：
  名称：

  4-Methoxy-N-[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide: A Potent and Selective Agonist of S1P₁

  摘要：

  The sphingosine-1-phosphate-1 receptor (S1P(1)) and its endogenous ligand sphingosine-1-phosphate (S1P) cooperatively regulate lymphocyte trafficking from the lymphatic system. Herein, we disclose 4-methoxy-N[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide (8), an uncommon example of a synthetic S1P(1) agonist lacking a polar headgroup, which is shown to effect dramatic reduction of circulating lymphocytes (POC = -78%) in rat 24 h after a single oral dose (1 mg/kg). The excellent potency that 8 exhibits toward S1P(1) (EC50 = 0.035 mu M, 96% efficacy) and the >100-fold selectivity that it displays against receptor subtypes S1P(2-5) suggest that it may serve as a valuable tool to understand the clinical relevance of selective S1P(1) agonism.

  DOI：

  10.1021/ml2001399
• 作为产物：
  描述：

  三正丁基2-吡啶基锌 、 3-三氟甲基-4-溴苯胺 在 四(三苯基膦)钯 作用下， 以 1,4-二氧六环 为溶剂， 反应 72.0h， 以88%的产率得到4-(pyridin-2-yl)-3-(trifluoromethyl)benzenamine
  参考文献：
  名称：

  4-Methoxy-N-[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide: A Potent and Selective Agonist of S1P₁

  摘要：

  The sphingosine-1-phosphate-1 receptor (S1P(1)) and its endogenous ligand sphingosine-1-phosphate (S1P) cooperatively regulate lymphocyte trafficking from the lymphatic system. Herein, we disclose 4-methoxy-N[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide (8), an uncommon example of a synthetic S1P(1) agonist lacking a polar headgroup, which is shown to effect dramatic reduction of circulating lymphocytes (POC = -78%) in rat 24 h after a single oral dose (1 mg/kg). The excellent potency that 8 exhibits toward S1P(1) (EC50 = 0.035 mu M, 96% efficacy) and the >100-fold selectivity that it displays against receptor subtypes S1P(2-5) suggest that it may serve as a valuable tool to understand the clinical relevance of selective S1P(1) agonism.

  DOI：

  10.1021/ml2001399

文献信息

• Quinolinone-based agonists of S1P1: Use of a N-scan SAR strategy to optimize in vitro and in vivo activity
  作者：Lewis D. Pennington、Michael D. Croghan、Kelvin K.C. Sham、Alexander J. Pickrell、Paul E. Harrington、Michael J. Frohn、Brian A. Lanman、Anthony B. Reed、Matthew R. Lee、Han Xu、Michele McElvain、Yang Xu、Xuxia Zhang、Michael Fiorino、Michelle Horner、Henry G. Morrison、Heather A. Arnett、Christopher Fotsch、Andrew S. Tasker、Min Wong、Victor J. Cee

  DOI：10.1016/j.bmcl.2011.10.085

  日期：2012.1

  We reveal how a N-scan SAR strategy (systematic substitution of each CH group with a N atom) was employed for quinolinone-based S1P(1) agonist 5 to modulate physicochemical properties and optimize in vitro and in vivo activity. The diaza-analog 17 displays improved potency (hS1P(1) RI; 17: EC50 = 0.020 mu M, 120% efficacy; 5: EC50 = 0.070 mu M, 110% efficacy) and selectivity (hS1P(3) Ca2+ flux; 17: EC50 >25 mu M; 5: EC50 = 1.5 mu M, 92% efficacy), as well as enhanced pharmacokinetics (17: CL = 0.15 L/h/kg, V-dss = 5.1 L/kg, T-1/2 = 24 h, % F = 110; 5: CL = 0.93 L/h/kg, V-dss = 11 L/kg, T-1/2 = 15 h, % F = 60) and pharmacodynamics (17: 1.0 mg/kg po, 24 h PLC POC = -67%; 5: 3 mg/kg po, 24 h PLC POC = -51%) in rat. (C) 2011 Elsevier Ltd. All rights reserved.