1-hydroxynaphthalene-2-carboxylic acid dibenzylamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-hydroxynaphthalene-2-carboxylic acid dibenzylamide
• 英文别名: N,N-dibenzyl-1-hydroxy-2-naphthamide；N,N-dibenzyl-1-hydroxynaphthalene-2-carboxamide
• 化学式: C₂₅H₂₁NO₂
• 分子量: 367.447
• InChiKey: WNTYDEKGVIJHAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  二苄胺 、 1-羟基-2-萘甲酸 在 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以24%的产率得到1-hydroxynaphthalene-2-carboxylic acid dibenzylamide
  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

• US4066403A
  申请人：——

  公开号：US4066403A

  公开（公告）日：1978-01-03
• US4284704A
  申请人：——

  公开号：US4284704A

  公开（公告）日：1981-08-18
• USRE30267E
  申请人：——

  公开号：USRE30267E

  公开（公告）日：1980-05-06
• 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.