3-butyryl-4-(2-methylphenylamino)-8-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)quinoline

• 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-butyryl-4-(2-methylphenylamino)-8-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)quinoline
• 英文别名: 1-[8-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]-4-(2-methylanilino)quinolin-3-yl]butan-1-one
• 化学式: C₂₆H₃₂N₂O₅
• 分子量: 452.55
• InChiKey: MMQIHPMIJVLHMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  33
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  89.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-butyryl-4-chloro-8-hydroxyquinoline 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 73.0h， 生成 3-butyryl-4-(2-methylphenylamino)-8-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)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

文献信息

• 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.

  该文段的中文翻译如下：替代4-氨基喹唑啉衍生物，是胃酸分泌的抑制剂。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-acyl quinoline derivatives and their use as inhibitors of gastric acid secretion
  申请人：SmithKline Beecham Intercredit B.V.

  公开号：EP0330485A1

  公开（公告）日：1989-08-30

  Compounds of structure (I) in which R1 is hydrogen, C1-6alkyl, C1-6alkoxy, C1-6al- koxyC1-6-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; Ci-salka- noyl or trifluoromethyl; m is 1, 2 or 3; p is 0 to 4; R3 is hydroxyC1-6alkyl, polyhydroxyC1-6alkyl, C1-6alkoxy1-6alkyl, hy- droxyC1-6alkoxy, polyhydroxyC1-6alkoxy, C1-6alkoxyC1-6alkoxy or hydroxyC1-6alkoxyC1-6alkoxy; and R4 is hydrogen, hydroxy, Ci-salkyl, 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.

  结构(I)的化合物 其中 R1 是氢、C1-6烷基、C1-6烷氧基、C1-6al- koxyC1-6-烷基、C3-6 环烷基、C3-6 环烷基 C1-6烷基、苯基、苯基 C1-6烷基，苯基基团被任选取代；R2 是氢、C1-6烷基、C1-6烷氧基、氨基、C1-6-烷硫基、卤素、氰基、羟基、氨基甲酰基、羧基、Ci-salka- noyl 或三氟甲基；m 是 1、2 或 3；p 是 0 至 4；R3 是羟基 C1-6烷基、多羟基 C1-6烷基、C1-6烷氧基 C1-6烷基、羟基 C1-6烷氧基、多羟基 C1-6烷氧基、C1-6烷氧基 C1-6烷氧基或羟基 C1-6烷氧基 C1-6烷氧基；以及 R4 是氢、羟基、Ci-烷基或 C1-6烷氧基、它们的制备工艺、制备它们时有用的中间体、含有它们的药物组合物以及它们作为胃酸分泌抑制剂在治疗中的用途。
• US5089504A
  申请人：——

  公开号：US5089504A

  公开（公告）日：1992-02-18
• US5432182A
  申请人：——

  公开号：US5432182A

  公开（公告）日：1995-07-11
• [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.