N-(1H-indol-6-yl)-4-oxo-1,4-dihydroquinoline-3-sulfonamide

• 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: N-(1H-indol-6-yl)-4-oxo-1,4-dihydroquinoline-3-sulfonamide
• 英文别名: 1,4-Dihydro-N-1H-indol-6-yl-4-oxo-3-quinolinesulfonamide；N-(1H-indol-6-yl)-4-oxo-1H-quinoline-3-sulfonamide
• 化学式: C₁₇H₁₃N₃O₃S
• 分子量: 339.375
• InChiKey: LEQHTMLQCVBNDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  99.4
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-羟基喹啉 在 吡啶 、 氯磺酸 作用下， 反应 6.0h， 生成 N-(1H-indol-6-yl)-4-oxo-1,4-dihydroquinoline-3-sulfonamide
  参考文献：
  名称：

  Discovery of N-(2,4-Di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, Ivacaftor), a Potent and Orally Bioavailable CFTR Potentiator

  摘要：

  Quinolinone-3-carboxamide 1, a novel CFTR potentiator, was discovered using high-throughput screening in NIH-3T3 cells expressing the F508del-CFTR mutation. Extensive medicinal chemistry and iterative structure-activity relationship (SAR) studies to evaluate potency, selectivity, and pharmacokinetic properties resulted in the identification of N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, 48, ivacaftor), an investigational drug candidate approved by the FDA for the treatment of CF patients 6 years of age and older carrying the G551D mutation.

  DOI：

  10.1021/jm5012808

文献信息

• Discovery of <i>N</i>-(2,4-Di-<i>tert</i>-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, Ivacaftor), a Potent and Orally Bioavailable CFTR Potentiator
  作者：Sabine Hadida、Fredrick Van Goor、Jinglan Zhou、Vijayalaksmi Arumugam、Jason McCartney、Anna Hazlewood、Caroline Decker、Paul Negulescu、Peter D. J. Grootenhuis

  DOI：10.1021/jm5012808

  日期：2014.12.11

  Quinolinone-3-carboxamide 1, a novel CFTR potentiator, was discovered using high-throughput screening in NIH-3T3 cells expressing the F508del-CFTR mutation. Extensive medicinal chemistry and iterative structure-activity relationship (SAR) studies to evaluate potency, selectivity, and pharmacokinetic properties resulted in the identification of N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, 48, ivacaftor), an investigational drug candidate approved by the FDA for the treatment of CF patients 6 years of age and older carrying the G551D mutation.