4-(N-methylphenylamino)-2-(2-methylphenylamino)-8-methoxy quinazoline | 124309-45-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-(N-methylphenylamino)-2-(2-methylphenylamino)-8-methoxy quinazoline
• 英文别名: 4-(N-Methylphenylamino)-2-(2-methylphenylamino)-8-methoxyquinazoline；8-methoxy-4-N-methyl-2-N-(2-methylphenyl)-4-N-phenylquinazoline-2,4-diamine
• CAS: 124309-45-1
• 化学式: C₂₃H₂₂N₄O
• 分子量: 370.454
• InChiKey: LPRAAPHEPRYBLH-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：
  0.13
• 拓扑面积：
  50.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(N-methylphenylamino)-2-(2-methylphenylamino)-8-methoxy quinazoline 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以38%的产率得到8-hydroxy-4-(N-methylphenylamino)-2-<(2-methylphenyl)amino>quinazoline
  参考文献：
  名称：

  Reversible Inhibitors of the Gastric (H+/K+)-ATPase. 5. Substituted 2,4-Diaminoquinazolines and Thienopyrimidines

  摘要：

  Quinazolines bearing a secondary 4-(arylamino) substituent demonstrate an SAR for inhibition of the gastric (H+/K+)-ATPase different from the previously described 3-acylquinolines, suggesting that, although these compounds are also K+-competitive, they probably bind to the enzyme in a different orientation. Compounds bearing a tertiary 4-(arylamino) substituent, however, in particular 4-(N-methylarylamino), appear to possess an SAR quite similar to the 3-acylquinolines. We show that this arises from the effect of the N-methylation, which is to orientate the 4-(arylamino) substituent syn to C-5, analogous to the 3-acylquinolines. Compounds possessing both a 4-(N-methylarylamino) substituent and a 2-(arylamino) substituent proved to be very potent, K+-competitive inhibitors of K+-stimulated ATPase activity with K-i values down to 12 nM. Some compounds also proved to be effective inhibitors of stimulated acid secretion in both the rat and dog when dosed intravenously. However, although a number of these demonstrated activity after oral administration in the dog, the level and variability precluded further evaluation.

  DOI：

  10.1021/jm00014a027

文献信息

• Substituted quinazoline derivatives for use in gastrointestinal diseases
  申请人：Smithkline Beecham Intercredit B.V.

  公开号：US05064833A1

  公开（公告）日：1991-11-12

  2,4-diaminoquinazoline compounds are inhibitors of the H.sup.+ K.sup.+ ATPase enzyme and useful for the treatment of diseases of the stomach based on excessive gastric acid secretion. A compound of the invention is 2-[2-methyl-4-fluorophenyl)amino]-4-(N-methylphenylamino)quinazoline.

  2,4-二氨基喹嗪化合物是H.sup.+ K.sup.+ ATPase酶的抑制剂，可用于治疗基于胃酸分泌过多的胃病。本发明的一种化合物是2-[2-甲基-4-氟苯基)氨基]-4-(N-甲基苯基氨基)喹嗪。
• Quinazoline derivatives
  申请人：SmithKline Beecham Intercredit B.V.

  公开号：EP0322133B1

  公开（公告）日：1991-05-22
• US5064833A
  申请人：——

  公开号：US5064833A

  公开（公告）日：1991-11-12
• WO1989005297A1
  申请人：——

  公开号：WO1989005297A1

  公开（公告）日：1989-06-15