2-[1-(2-Acetyl-phenylamino)-meth-(Z)-ylidene]-3-oxo-hexanoic acid ethyl ester | 126058-94-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[1-(2-Acetyl-phenylamino)-meth-(Z)-ylidene]-3-oxo-hexanoic acid ethyl ester
• 英文别名: ethyl 2-[(2-acetylanilino)methylidene]-3-oxohexanoate
• CAS: 126058-94-4
• 化学式: C₁₇H₂₁NO₄
• 分子量: 303.358
• InChiKey: ZFVIIAMDTUUMPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  72.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[1-(2-Acetyl-phenylamino)-meth-(Z)-ylidene]-3-oxo-hexanoic acid ethyl ester 以 二苯醚 为溶剂， 反应 3.5h， 以64%的产率得到3-butyryl-8-acetyl-4(1H)-quinolone
  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：

  丁酰乙酸乙酯 在 乙酸酐 作用下， 反应 0.17h， 生成 2-[1-(2-Acetyl-phenylamino)-meth-(Z)-ylidene]-3-oxo-hexanoic acid ethyl ester
  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

文献信息

• 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.

  公式如下：##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，C.sub.1-6酰基或三氟甲基；m为1至3；R.sup.3是氢，C.sub.1-6烷基，苯基，C.sub.1-6烷氧基，C.sub.1-6烷基硫基，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是氢；或其盐可用作胃酸分泌抑制剂。