ethyl 8-methoxy-4-[(2-methylphenyl)amino]-3-quinolinecarboxylate hydrochloride | 77156-86-6

• 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: ethyl 8-methoxy-4-[(2-methylphenyl)amino]-3-quinolinecarboxylate hydrochloride
• 英文别名: ethyl 8-methoxy-4-(2-methylanilino)quinoline-3-carboxylate;hydrochloride
• CAS: 77156-86-6
• 化学式: C₂₀H₂₀N₂O₃*ClH
• 分子量: 372.851
• InChiKey: DXCCJYWRCAJAGW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.89
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  60.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 8-methoxy-4-[(2-methylphenyl)amino]-3-quinolinecarboxylate hydrochloride 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以37%的产率得到(8-Methoxy-4-o-tolylamino-quinolin-3-yl)-methanol
  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
• 作为产物：
  描述：

  4-氯-8-甲氧基喹啉-3-甲酸乙酯 、 邻甲苯胺 在 异丙醚 、 二氯甲烷 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 ethyl 8-methoxy-4-[(2-methylphenyl)amino]-3-quinolinecarboxylate hydrochloride
  参考文献：
  名称：

  4-Amino-3-quinolinecarboxylic acids and esters-antisecretory anti-ulcer

  摘要：

  本发明揭示了一种利用某些4-氨基-3-喹啉羧酸和酯来降低胃酸度和治疗消化性溃疡的方法以及制药组合物。本方法所依赖的抗分泌活性的化合物的例子是新型化合物乙酰氧基-8-甲氧基-4-[(2-甲基苯基)氨基]-3-喹啉羧酸乙酯，其化学式为：##STR1##

  公开号：

  US04343804A1

文献信息

• US4343804A
  申请人：——

  公开号：US4343804A

  公开（公告）日：1982-08-10
• 4-Amino-3-quinolinecarboxylic acids and esters-antisecretory anti-ulcer
  申请人：A. H. Robins Company, Inc.

  公开号：US04343804A1

  公开（公告）日：1982-08-10

  A method of reducing gastric acidity and treating peptic ulcers and pharmaceutical compositions therefor with certain 4-amino-3-quinolinecarboxylic acids and esters are disclosed. Illustrative of compounds useful in the method which relies on activity as antisecretory activity is the novel compound ethyl 8-methoxy-4-[(2-methylphenyl)amino]-3-quinolinecarboxylate which has the formula: ##STR1##

  公开了一种降低胃酸度和治疗消化性溃疡的方法以及用于此的药物组合物，该方法使用某些4-氨基-3-喹啉羧酸及其酯。作为依赖于抗分泌活性的方法中有用的化合物的一个例子，是新化合物乙基8-甲氧基-4-[(2-甲基苯基)氨基]-3-喹啉羧酸酯，其化学式如下： ##STR1##
• 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.