N-(3-amino-4-methylphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide

• 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: N-(3-amino-4-methylphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide
• 英文别名: N-(3-amino-4-methylphenyl)-4-oxo-1H-quinoline-3-carboxamide；N-(3-amino-4-methyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide
• 化学式: C₁₇H₁₅N₃O₂
• 分子量: 293.325
• InChiKey: LNQQUYVEYRCVQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  84.2
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(3-amino-4-methylphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide 、 乙酰氯 在 N,N-二异丙基乙胺 、 哌啶 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.0h， 以11%的产率得到N-(3-acetylamino-4-methylphenyl)-4-oxo-1H-quinoline-3-carboxamide
  参考文献：
  名称：

  Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases

  摘要：

  本发明涉及含有上皮钠通道活性抑制剂与至少一种ABC转运蛋白调节剂化合物（A式、B式、C式或D式）的药物组合物。该发明还涉及这些药物配方，以及使用这些组合物治疗CFTR介导的疾病，特别是囊性纤维化的方法。

  公开号：

  US20150231142A1
• 作为产物：
  描述：

  2,4-二氨基甲苯 、 4-氧代-1,4-二氢喹啉-3-羧酸 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以43%的产率得到N-(3-amino-4-methylphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide
  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

• COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES
  申请人：Van Goor Fredrick F.

  公开号：US20110098311A1

  公开（公告）日：2011-04-28

  The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.

  本发明涉及包含上皮钠通道活性抑制剂与至少一种ABC转运蛋白调节剂化合物（A式、B式、C式或D式）的药物组合物。该发明还涉及这些药物配方，以及使用这些组合物治疗CFTR介导的疾病，特别是囊性纤维化的方法。
• MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS
  申请人：Sheth Urvi

  公开号：US20120309758A1

  公开（公告）日：2012-12-06

  The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

  本发明涉及调节ATP结合盒（“ABC”）转运蛋白或其片段的调节剂，包括囊性纤维化跨膜传导调节蛋白，以及相关的组合物和方法。本发明还涉及使用这些调节剂治疗ABC转运蛋白介导的疾病的方法。
• Modulators of ATP-binding cassette transporters
  申请人：Hadida-Ruah Sara

  公开号：US20060074075A1

  公开（公告）日：2006-04-06

  The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

  本发明涉及ATP结合盒（“ABC”）转运蛋白或其片段的调节剂，包括囊性纤维化跨膜传导调节因子及其组合物和使用这些调节剂治疗ABC转运蛋白介导的疾病的方法。
• Modulators of ATP-Binding Cassette Transporters
  申请人：Hadida-Ruah Sara

  公开号：US20130035327A1

  公开（公告）日：2013-02-07

  The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

  本发明涉及ATP结合盒（“ABC”）转运蛋白或其片段的调节剂，包括囊性纤维化跨膜导电调节器，以及其组成物和使用这些调节剂的方法。本发明还涉及使用这些调节剂治疗ABC转运蛋白介导的疾病的方法。
• COMPOUNDS USEFUL IN CFTR ASSAYS AND METHODS THEREWITH
  申请人：Singh Ashvani K.

  公开号：US20090246820A1

  公开（公告）日：2009-10-01

  The present invention relates to compounds useful in CFTR assays. The present invention also relates to compounds useful in monitoring CFTR activity in therapies for CFTR-mediated diseases. The present invention also provides an assay for use in measuring CFTR correction.

  本发明涉及在CFTR测定中有用的化合物。本发明还涉及在治疗CFTR介导的疾病中监测CFTR活性的有用化合物。本发明还提供了一种用于测量CFTR校正的测定方法。