3-butyryl-4-(4-hydroxy-3-fluorophenylamino)-8-methoxyquinoline

• 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-(4-hydroxy-3-fluorophenylamino)-8-methoxyquinoline
• 英文别名: 3-Butyryl-4-(3-fluoro-4-hydroxyphenylamino)-8-methoxyquinoline；1-[4-(3-fluoro-4-hydroxyanilino)-8-methoxyquinolin-3-yl]butan-1-one
• 化学式: C₂₀H₁₉FN₂O₃
• 分子量: 354.381
• InChiKey: OZFRQHOJAFPGIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  71.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  丁酰乙酸乙酯 在 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 8.0h， 生成 3-butyryl-4-(4-hydroxy-3-fluorophenylamino)-8-methoxyquinoline
  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.

  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。
• 4-Amino-3-acylquinoline derivatives and their use as inhibitors of gastric secretion
  申请人：SMITHKLINE BEECHAM INTERCREDIT B.V.

  公开号：EP0342775B1

  公开（公告）日：1993-09-15
• US5143920A
  申请人：——

  公开号：US5143920A

  公开（公告）日：1992-09-01
• [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：WO1989008105A1

  公开（公告）日：1989-09-08

  (EN) Compounds of structure (I), in which R1 is hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6-alkyl, C3-6cycloalkyl, C3-6cycloalkylC1-6alkyl, phenylC1-6alkyl, the phenyl group being optionally substituted; R2 is hydrogen, C1-6alkyl, C1-6alkoxy, amino, C1-6alkylthio, halogen, cyano, hydroxy, C1-6alkanoyl or trifluoromethyl; m is 1 to 3; R3 is hydrogen, C1-6alkyl, phenyl, C1-6alkoxy, C1-6alkylthio, C1-6alkanoyl, amino, C1-6alkylamino, di-C1-6alkylamino, halogen, trifluoromethyl or cyano; n is 1 or 2; and R4O- is hydroxy or a bioprecursor of a hydroxy group, processes for their preparation, intermediates useful in their preparation, pharmaceutical compositions containing them and their use in therapy as gastric acid secretion inhibitors.(FR) Les composés décrits sont représentés par la structure (I); où R1 représente l'hydrogène, un C1-6alkyle, un C1-6alkoxy, un C1-6alkoxyC1-6alkyle, un C3-6cycloakyle, un C3-6cycloalkylC1-6alkyle, un phénylC1-6alkyle, le groupe phényle étant éventuellement substitué; R2 représente l'hydrogène, un C1-6alkoxy, un amino, un C1-6alkylthio, un halogène, un cyano, un hydroxy, un C1-¿6alkanoyle ou un trifluorométhyle; m est compris entre 1 et 3; R3 représente l'hydrogène, un C1-6alkyle, un phényle, un C1-6alkoxy, un C1-6alkylthio, un C1-6alkanoyle, un amino, un C1-6alkylamino, un di-C1-6alkylamino, un halogène, un trifluorométhyle ou un cyano; n is égal à 1 ou 2; et R4O- représente un hydroxy ou un bioprécurseur d'un groupe hydroxy. 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 sécrétion de l'acide gastrique sont également décrits.
• 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.