1-methyl-4-oxo-N-[5-phenyl-4-(trifluoromethyl)pyridin-2-yl]quinoline-3-carboxamide | 1356829-35-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-methyl-4-oxo-N-[5-phenyl-4-(trifluoromethyl)pyridin-2-yl]quinoline-3-carboxamide
• CAS: 1356829-35-0
• 化学式: C₂₃H₁₆F₃N₃O₂
• 分子量: 423.394
• InChiKey: HQHGWCLUVCPXGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  62.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-甲基-4-氧代-1,4-二氢喹啉-3-羧酸 、 5-Phenyl-4-(trifluoromethyl)pyridin-2-amine 在 N,N-二异丙基乙胺 作用下， 生成 1-methyl-4-oxo-N-[5-phenyl-4-(trifluoromethyl)pyridin-2-yl]quinoline-3-carboxamide
  参考文献：
  名称：

  Quinolinone-based agonists of S1P1: Use of a N-scan SAR strategy to optimize in vitro and in vivo activity

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2011.10.085

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.