4-<<3-butyryl-4-<(2-methylphenyl)amino>quinolin-8-yl>oxy>butanoic acid | 164861-03-4

• 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: 4-<<3-butyryl-4-<(2-methylphenyl)amino>quinolin-8-yl>oxy>butanoic acid
• CAS: 164861-03-4
• 化学式: C₂₄H₂₆N₂O₄
• 分子量: 406.481
• InChiKey: GSIFJCIIROMTIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.51
• 重原子数：
  30.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  88.52
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-氨基吡啶 、 4-<<3-butyryl-4-<(2-methylphenyl)amino>quinolin-8-yl>oxy>butanoic acid 在 4-吡咯烷基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 17.0h， 以93%的产率得到4-(3-Butyryl-4-o-tolylamino-quinolin-8-yloxy)-N-pyridin-4-yl-butyramide
  参考文献：
  名称：

  Reversible Inhibitors of the Gastric (H+/K+)-ATPase. 4. Identification of an Inhibitor with an Intermediate Duration of Action

  摘要：

  3-Acyl-4-(arylamino)quinolines were previously identified as gastric (H+/K+)-ATPase inhibitors, and clinical efficacy has been demonstrated for compound 3 (SK&F 96067). In the present study the further structure-activity relationship of this series is developed. Only a limited range of substituents are tolerated on the N-aryl ring or the 6- and 7-positions of the quinoline, and although hydroxylated derivatives were identified possessing markedly greater affinity for the enzyme, none of these proved to have adequate potency after oral dosing. In contrast, the 8-position of the quinoline ring proved suitable for a wide variety of substituents, allowing modification of physicochemical properties while retaining primary activity. This led to the identification of compound 4 (SK&F 97574), which combines good oral potency with a somewhat longer duration of action than 3 (though much shorter than covalent inhibitors such as omeprazole). This compound was selected for further development and evaluation in man.

  DOI：

  10.1021/jm00014a026
• 作为产物：
  描述：

  3-butyryl-4-chloro-8-hydroxyquinoline 在 氢氧化钾 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 为溶剂， 反应 19.0h， 生成 4-<<3-butyryl-4-<(2-methylphenyl)amino>quinolin-8-yl>oxy>butanoic acid
  参考文献：
  名称：

  Reversible Inhibitors of the Gastric (H+/K+)-ATPase. 4. Identification of an Inhibitor with an Intermediate Duration of Action

  摘要：

  3-Acyl-4-(arylamino)quinolines were previously identified as gastric (H+/K+)-ATPase inhibitors, and clinical efficacy has been demonstrated for compound 3 (SK&F 96067). In the present study the further structure-activity relationship of this series is developed. Only a limited range of substituents are tolerated on the N-aryl ring or the 6- and 7-positions of the quinoline, and although hydroxylated derivatives were identified possessing markedly greater affinity for the enzyme, none of these proved to have adequate potency after oral dosing. In contrast, the 8-position of the quinoline ring proved suitable for a wide variety of substituents, allowing modification of physicochemical properties while retaining primary activity. This led to the identification of compound 4 (SK&F 97574), which combines good oral potency with a somewhat longer duration of action than 3 (though much shorter than covalent inhibitors such as omeprazole). This compound was selected for further development and evaluation in man.

  DOI：

  10.1021/jm00014a026