[3-Butanoyl-4-(2-methylanilino)quinolin-8-yl]methyl 4-methoxybenzoate | 125526-06-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [3-Butanoyl-4-(2-methylanilino)quinolin-8-yl]methyl 4-methoxybenzoate
• CAS: 125526-06-9
• 化学式: C₂₉H₂₈N₂O₄
• 分子量: 468.552
• InChiKey: WUASQMOKYXVAML-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [3-Butanoyl-4-(2-methylanilino)quinolin-8-yl]methyl 4-methoxybenzoate 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 0.5h， 生成 3-butyryl-4-(2-methylphenylamino)-8-(hydroxymethyl)quinoline
  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 吡啶 、 乙酸酐 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 二苯醚 为溶剂， 反应 17.17h， 生成 [3-Butanoyl-4-(2-methylanilino)quinolin-8-yl]methyl 4-methoxybenzoate
  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

• [EN] 4-AMINO-3-ACYLQUINOLINE DERIVATIVES AND THEIR USE AS INHIBITORS OF GASTRIC SECRETION
  申请人：SMITHKLINE BECKMAN INTERCREDIT B.V.

  公开号：WO1989008104A1

  公开（公告）日：1989-09-08

  (EN) Compounds of structure (I), in which R1 is hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6-alkyl, C3-6cycloalkyl, C3-6cycloalkylC1-6alkyl, phenyl, phenylC1-6alkyl, the phenyl groups being optionally substituted; R2 is hydrogen, C1-6alkyl, C1-6alkoxy, amino, C1-6-alkylthio, halogen, cyano, hydroxy, carbamoyl, carboxy, C1-6alkanoyl or trifluoromethyl; m is 1, 2 or 3; p is 0 to 4; R3 is hydroxyC1-6alkyl, polyhydroxyC1-6alkyl, C1-6alkoxyC1-6alkyl, hydroxyC1-6alkoxy, polyhydroxy-C1-6alkoxy, C1-6alkoxyC1-6alkoxy or hydroxyC1-6alkoxy-C1-6alkoxy; and R4 is hydrogen, hydroxy, C1-6alkyl, or C1-6alkoxy, processes for their preparation, intermediates useful in their preparation, pharmaceutical compositions containing them and their use in therapy as inhibitors of gastric acid secretion.(FR) Les composés décrits sont représentés par la structure (I); où R1 représente l'hydrogène, un C1-6alkyle, un C1-6alcoxy, un C1-6alcoxyC1-6-alkyle, un C1-6cycloalkyle, un C3-6cycloalkylC1-6alkyle, un phényle, un phénylC1-6alkyle, les groupes phényle étant éventuellement substitués; R2 représente l'hydrogène, un C1-6alkyle, un C1-6alcoxy, un amino, un C1-6-alkylthio, un halogène, un cyano, un hydroxy, un carbamoyle, un carboxy, un C1-6alcanoyle ou un trifluorométhyle; m est égal à 1, 2 ou 3; p est compris entre 0 et 4; R3 représente un hydroxyC1-6alkyle, un polyhydroxyC1-6alkyle, un C1-6alcoxyC1-6alkyle, un hydroxyC1-6alcoxy, un polyhydroxyC1-6alcoxy, un C1-6alcoxyC1-6alcoxy ou un hydroxyC1-6alcoxyC1-6alcoxy; et R4 représente l'hydrogène, un hydroxy, un C1-6alkyle ou un C1-6alcoxy. Des procédés servant à la préparation de tels composés, des intermédiaires utiles dans cette préparation, des compositions pharmaceutiques contenant de tels composés et leur utilisation thérapeutique comme inhibiteurs de la sécrétion d'acide gastrique.
• Reversible Inhibitors of the Gastric (H+/K+)-ATPase. 4. Identification of an Inhibitor with an Intermediate Duration of Action
  作者：Colin A. Leach、Thomas H. Brown、Robert J. Ife、David J. Keeling、Michael E. Parsons、Colin J. Theobald、Kenneth J. Wiggall

  DOI：10.1021/jm00014a026

  日期：1995.7

  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.