1-methyl-4-oxo-3-((2-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)carbamoyl)-1,4-dihydroquinoline-8-carboxylic acid | 1351945-13-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-methyl-4-oxo-3-((2-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)carbamoyl)-1,4-dihydroquinoline-8-carboxylic acid
• 英文别名: 1-Methyl-4-oxo-3-[[4-phenyl-3-(trifluoromethyl)phenyl]carbamoyl]quinoline-8-carboxylic acid
• CAS: 1351945-13-5
• 化学式: C₂₅H₁₇F₃N₂O₄
• 分子量: 466.416
• InChiKey: QPBTWSQMEZASAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  86.7
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  8-氯-4-羟基-3-喹啉羧酸 在 sodium chlorite 、 sodium periodate 、 sodium dihydrogenphosphate 、 四氧化锇 、 2-甲基-2-丁烯 、 二(三叔丁基膦)钯 、 lithium hydroxide monohydrate 、 caesium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N-甲基吗啉氧化物 、 三乙胺 、 cesium fluoride 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 叔丁醇 为溶剂， 反应 65.5h， 生成 1-methyl-4-oxo-3-((2-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)carbamoyl)-1,4-dihydroquinoline-8-carboxylic acid
  参考文献：
  名称：

  Optimization of a Potent, Orally Active S1P₁ Agonist Containing a Quinolinone Core

  摘要：

  The optimization of a series of SIP, agonists with limited activity against S1P(3) is reported. A polar headgroup was used to improve the physicochemical and pharmacokinetic parameters of lead quinolinone 6. When dosed orally at 1 and 3 mg/kg, the azahydroxymethyl analogue 22 achieved statistically significant lowering of circulating blood lymphocytes 24 h postdose. In rats, a dose-proportional increase in exposure was measured when 22 was dosed orally at 2 and 100 mg/kg.

  DOI：

  10.1021/ml200252b

文献信息

• Optimization of a Potent, Orally Active S1P₁ Agonist Containing a Quinolinone Core
  作者：Paul E. Harrington、Michael D. Croghan、Christopher Fotsch、Mike Frohn、Brian A. Lanman、Lewis D. Pennington、Alexander J. Pickrell、Anthony B. Reed、Kelvin K. C. Sham、Andrew Tasker、Heather A. Arnett、Michael Fiorino、Matthew R. Lee、Michele McElvain、Henry G. Morrison、Han Xu、Yang Xu、Xuxia Zhang、Min Wong、Victor J. Cee

  DOI：10.1021/ml200252b

  日期：2012.1.12

  The optimization of a series of SIP, agonists with limited activity against S1P(3) is reported. A polar headgroup was used to improve the physicochemical and pharmacokinetic parameters of lead quinolinone 6. When dosed orally at 1 and 3 mg/kg, the azahydroxymethyl analogue 22 achieved statistically significant lowering of circulating blood lymphocytes 24 h postdose. In rats, a dose-proportional increase in exposure was measured when 22 was dosed orally at 2 and 100 mg/kg.