2-[1-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-phenylamino]-meth-(Z)-ylidene]-3-oxo-hexanoic acid ethyl ester | 135385-27-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-[1-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-phenylamino]-meth-(Z)-ylidene]-3-oxo-hexanoic acid ethyl ester
• 英文别名: ethyl 2-[[2-(1,3-dioxoisoindol-2-yl)anilino]methylidene]-3-oxohexanoate
• CAS: 135385-27-2
• 化学式: C₂₃H₂₂N₂O₅
• 分子量: 406.438
• InChiKey: JHBFUKJAYSKVSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.72
• 重原子数：
  30.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  92.78
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2-[1-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-phenylamino]-meth-(Z)-ylidene]-3-oxo-hexanoic acid ethyl ester 在 一水合肼 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 二苯醚 、 乙醇 为溶剂， 反应 4.25h， 生成 1-[8-Amino-4-(2,6-dimethyl-phenylamino)-quinolin-3-yl]-butan-1-one
  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-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-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

• 3-carbonyl-4-amino-8-substituted quinoline compounds useful in
  申请人：SmithKline Beecham Intercredit B.V.

  公开号：US05082841A1

  公开（公告）日：1992-01-21

  Aminoquinoline derivatives are described as inhibitors of the H.sup.+ K.sup.+ ATPase enzyme useful in the treatment of gastric acidity. A compound of the invention is 3-butyryl-4-(2-methylphenylamino)-8-(3-dimethylaminopropoxy)quinoline.

  氨基喹啉衍生物被描述为抑制H.sup.+ K.sup.+ ATPase酶的药物，可用于治疗胃酸过多。该发明的化合物是3-丁酰基-4-(2-甲基苯胺)-8-(3-二甲氨基丙氧基)喹啉。