3-isobutyryl-4-chloro-8-methoxy-quinoline | 115607-93-7

• 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: 3-isobutyryl-4-chloro-8-methoxy-quinoline
• 英文别名: 4-chloro-3-isobutyryl-8-methoxyquinoline；3-Isobutyryl-4-chloro-8-methoxyquinoline；1-(4-chloro-8-methoxyquinolin-3-yl)-2-methylpropan-1-one
• CAS: 115607-93-7
• 化学式: C₁₄H₁₄ClNO₂
• 分子量: 263.724
• InChiKey: JVZYGCSEZIPODV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-isobutyryl-4-chloro-8-methoxy-quinoline 在 三溴化硼 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 3-isobutyryl-4-(2-methylphenylamino)-8-hydroxyquinoline
  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：

  ethyl 3-<(2-methoxyphenyl)amino>acrylate 在 sodium hydride 、 三氯氧磷 作用下， 以 二苯醚 、 氯仿 为溶剂， 反应 18.0h， 生成 3-isobutyryl-4-chloro-8-methoxy-quinoline
  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

• 4-amino-3-carbonyl substituted quinolines
  申请人：Smith Kline & French Laboratories Limited

  公开号：US04806549A1

  公开（公告）日：1989-02-21

  This invention relates to novel substituted 4-aminoquinoline derivatives which are inhibitors of gastric acid secretion in mammals. A compound of the invention is 3-butyryl-4-(2-methylphenylamino)-8-methoxyquinoline.

  这项发明涉及新型的取代4-氨基喹啉衍生物，它们是哺乳动物胃酸分泌抑制剂。该发明的化合物是3-丁酰基-4-(2-甲基苯胺基)-8-甲氧基喹啉。
• Substituted 4-aminoquinoline derivatives as gastric secretion inhibitors
  申请人：SmithKline Beckman Intercredit B.V.

  公开号：US05143920A1

  公开（公告）日：1992-09-01

  Substituted 4-aminoquinazoline derivatives of the formula: ##STR1## wherein R.sup.1 is hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkoxy C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyl C.sub.1-6 alkyl, phenyl C.sub.1-6 alkyl, the phenyl group being optionally substituted; R.sup.2 is hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, amino, C.sub.1-6 alkylthio, halogen, cyano, hydroxy, C.sub.1-6 alkanoyl or trifuromethyl; m is 1 to 3; R.sup.3 is hydrogen, C.sub.1-6 alkyl, phenyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, C.sub.1-6 alkanoyl, amino, C.sub.1-6 alkylamino, ci-C.sub.1-6 alkylamino, halogen, trifluoromethyl or cyano; n is 1 or 2; and R.sup.4 is hydrogen; or a salt thereof are useful as inhibitors of gastric acid secretion.

  该公式中的4-氨基喹唑啉衍生物：其中R.sup.1为氢、C.sub.1-6烷基、C.sub.1-6烷氧基、C.sub.1-6烷氧基C.sub.1-6烷基、C.sub.3-6环烷基、C.sub.3-6环烷基C.sub.1-6烷基、苯基C.sub.1-6烷基，苯基可选择性取代；R.sup.2为氢、C.sub.1-6烷基、C.sub.1-6烷氧基、氨基、C.sub.1-6烷硫基、卤素、氰基、羟基、C.sub.1-6酰基或三氟甲基；m为1至3；R.sup.3为氢、C.sub.1-6烷基、苯基、C.sub.1-6烷氧基、C.sub.1-6烷硫基、C.sub.1-6烷酰基、氨基、C.sub.1-6烷基氨基、ci-C.sub.1-6烷基氨基、卤素、三氟甲基或氰基；n为1或2；R.sup.4为氢；或其盐可用作抑制胃酸分泌的药物。
• Substituted 4-aminoquinoline derivatives as gastric acid secretion
  申请人：SmithKline Beckman Intercredit B.V.

  公开号：US05089504A1

  公开（公告）日：1992-02-18

  Substituted 4-aminoquinazoline derivatives of the formula: ##STR1## in which R.sup.1 is hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkoxyC.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkylC.sub.1-6 alkyl, phenylC.sub.1-6 alkyl, the phenyl group being optionally substituted; R.sup.2 is hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, amino, C.sub.1-6 alkylthio, halogen, cyano, hydroxy, carbamoyl, carboxy, C.sub.1-6 alkanoyl or trifluoromethyl; m is 1 to 3; p is 0 to 4; R.sup.3 is COR.sup.4 ; R.sup.4 is hydroxy, C.sub.1-6 alkoxy, or NR.sup.5 R.sup.6 ; R.sup.5 and R.sup.6 are each hydrogen or C.sub.1-6 alkyl or together with the nitrogen atom to which they are attached form a heterocyclic ring; and R.sup.7 is hydrogen, C.sub.1-6 alkoxy or C.sub.1-6 alkyl; or a salt thereof.

  公式为：##STR1##其中R.sup.1是氢，C.sub.1-6烷基，C.sub.1-6烷氧基，C.sub.1-6烷氧基C.sub.1-6烷基，C.sub.3-6环烷基，C.sub.3-6环烷基C.sub.1-6烷基，苯基C.sub.1-6烷基，苯基可以选择性地被取代；R.sup.2是氢，C.sub.1-6烷基，C.sub.1-6烷氧基，氨基，C.sub.1-6烷基硫基，卤素，氰基，羟基，氨甲酰基，羧基，C.sub.1-6烷酰基或三氟甲基；m为1至3；p为0至4；R.sup.3是COR.sup.4；R.sup.4是羟基，C.sub.1-6烷氧基或NR.sup.5 R.sup.6；R.sup.5和R.sup.6分别是氢或C.sub.1-6烷基，或者与它们连接的氮原子一起形成杂环环；R.sup.7是氢，C.sub.1-6烷氧基或C.sub.1-6烷基；或其盐。
• Compounds substituted quinoline derivatives
  申请人：SmithKline Beecham Intercredit B.V.

  公开号：US05432182A1

  公开（公告）日：1995-07-11

  Substituted 4-aminoquinazoline derivatives which are inhibitors of gastric acid secretion. A compound of the invention are the salts of strong acids of 3-butyryl-4-(2-methylphenylamino)-8-(hydroxymethyl)quinoline.

  替代4-氨基喹唑啉衍生物是胃酸分泌抑制剂。该发明的化合物是3-丁酰基-4-(2-甲基苯胺基)-8-(羟甲基)喹啉的强酸盐。
• 4-Amino-3-carbonyl substituted quinolines as inhibitors of gastric acid
  申请人：SmithKline & French Laboratories Limited

  公开号：US04806550A1

  公开（公告）日：1989-02-21

  This invention relates to novel substituted 4-aminoquinoline derivatives which are inhibitors of gastric acid secretion in mammals. A compound of the invention is 3-butyryl-4-(2-methylphenylamino)-8-methoxyquinoline.

  本发明涉及一种新型的取代的4-氨基喹啉衍生物，该衍生物是哺乳动物胃酸分泌抑制剂。本发明的一种化合物是3-丁酰基-4-(2-甲基苯胺基)-8-甲氧基喹啉。