2-amino-8-methyl-4-(2-methylphenylamino)quinazoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-amino-8-methyl-4-(2-methylphenylamino)quinazoline
• 英文别名: 8-Methyl-N*4*-o-tolyl-quinazoline-2,4-diamine；8-methyl-4-N-(2-methylphenyl)quinazoline-2,4-diamine
• 化学式: C₁₆H₁₆N₄
• 分子量: 264.33
• InChiKey: AIORFOSTLDWCOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  63.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,4-二氯-8-甲基喹唑啉 在 氨 、 sodium acetate 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 99.0h， 生成 2-amino-8-methyl-4-(2-methylphenylamino)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.

  2,4-二氨基喹唑啉化合物是H.sup.+ K.sup.+ ATP酶的抑制剂，对基于胃酸分泌过多的胃病的治疗有用。该发明的化合物是2-[2-甲基-4-氟苯基)氨基]-4-(N-甲基苯胺基)喹唑啉。
• 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