1-[8-Methoxy-4-(2-methylanilino)quinolin-3-yl]butan-1-ol | 142782-09-0

• 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: 1-[8-Methoxy-4-(2-methylanilino)quinolin-3-yl]butan-1-ol
• CAS: 142782-09-0
• 化学式: C₂₁H₂₄N₂O₂
• 分子量: 336.434
• InChiKey: QAGWRXTZANBLKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  54.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-[8-甲氧基-4-[(2-甲基苯基)氨基]喹啉-3-基]丁烷-1-酮 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以68%的产率得到1-[8-Methoxy-4-(2-methylanilino)quinolin-3-yl]butan-1-ol
  参考文献：
  名称：

  Reversible inhibitors of the gastric (H+/K+)-ATPase. 3. 3-Substituted-4-(phenylamino)quinolines

  摘要：

  Previously, gastric (H+/K+)-ATPase inhibitors such as 2 have been prepared as analogues of 1a on the presumption that the 3-carbethoxy substituent plays a key role in establishing the orientation of the 4-arylamino group. In this paper we explore further the contribution made to activity by the quinoline 3-substituent. We show th bearing such a substituent, only a particular combination of properties provides high activity, both in as inhibitors of gastric acid secretion in vivo. The ability of the substituent to affect activity by restricting rotation about the C(quin)-N bond through a combination of both a pi-electron withdrawal and hydrogen bonding is supported by the current study. However, high activity is only achieved if the effect of this group on the quinoline pK(a) is kept to a minimum. 3-Acyl substituents provide an optimum combination of electronic properties. From this series, compound 17c (SK&F 96067) was shown to be a potent inhibitor of histamine-stimulated gastric acid secretion oral dosing in the Heidenhain pouch dog and was selected for further development and evaluation in man.

  DOI：

  10.1021/jm00096a018

文献信息

• Reversible inhibitors of the gastric (H+/K+)-ATPase. 3. 3-Substituted-4-(phenylamino)quinolines
  作者：Robert J. Ife、Thomas H. Brown、David J. Keeling、Colin A. Leach、Malcolm L. Meeson、Michael E. Parsons、David R. Reavill、Colin J. Theobald、Kenneth J. Wiggall

  DOI：10.1021/jm00096a018

  日期：1992.9

  Previously, gastric (H+/K+)-ATPase inhibitors such as 2 have been prepared as analogues of 1a on the presumption that the 3-carbethoxy substituent plays a key role in establishing the orientation of the 4-arylamino group. In this paper we explore further the contribution made to activity by the quinoline 3-substituent. We show th bearing such a substituent, only a particular combination of properties provides high activity, both in as inhibitors of gastric acid secretion in vivo. The ability of the substituent to affect activity by restricting rotation about the C(quin)-N bond through a combination of both a pi-electron withdrawal and hydrogen bonding is supported by the current study. However, high activity is only achieved if the effect of this group on the quinoline pK(a) is kept to a minimum. 3-Acyl substituents provide an optimum combination of electronic properties. From this series, compound 17c (SK&F 96067) was shown to be a potent inhibitor of histamine-stimulated gastric acid secretion oral dosing in the Heidenhain pouch dog and was selected for further development and evaluation in man.