3-butyryl-4-(2-methylphenylamino)-8-(hydroxymethyl)quinoline | 125500-21-2

• 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-(hydroxymethyl)quinoline
• 英文别名: 3-Butyryl-4-(2-methylphenylamino)-8-hydroxymethylquinoline；1-[8-(hydroxymethyl)-4-(2-methylanilino)quinolin-3-yl]butan-1-one
• CAS: 125500-21-2
• 化学式: C₂₁H₂₂N₂O₂
• 分子量: 334.418
• InChiKey: XILHSDVWNVEOTF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  62.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-butyryl-4-(2-methylphenylamino)-8-(hydroxymethyl)quinoline 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 3-butyryl-4-(2-methylphenylamino)-8-(1-hydroxyethyl)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：

  2-(乙氧基亚甲基)-3-氧代-己酸乙酯 在 吡啶 、 氢氧化钾 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 二苯醚 、 乙醇 为溶剂， 反应 17.67h， 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

文献信息

• Substituted 4-aminoquinoline derivatives as gastric acid secretion
  申请人：SmithKline Beckman Intercredit B.V.

  公开号：US05089504A1

  公开（公告）日：1992-02-18

  Substituted 4-aminoquinazoline derivatives of the formula: ##STR1## in which R.sup.1 is hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkoxyC.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkylC.sub.1-6 alkyl, phenylC.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, carbamoyl, carboxy, C.sub.1-6 alkanoyl or trifluoromethyl; m is 1 to 3; p is 0 to 4; R.sup.3 is COR.sup.4 ; R.sup.4 is hydroxy, C.sub.1-6 alkoxy, or NR.sup.5 R.sup.6 ; R.sup.5 and R.sup.6 are each hydrogen or C.sub.1-6 alkyl or together with the nitrogen atom to which they are attached form a heterocyclic ring; and R.sup.7 is hydrogen, C.sub.1-6 alkoxy or C.sub.1-6 alkyl; or a salt thereof.

  公式为：##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，氨甲酰基，羧基，C.sub.1-6烷酰基或三氟甲基；m为1至3；p为0至4；R.sup.3是COR.sup.4；R.sup.4是羟基，C.sub.1-6烷氧基或NR.sup.5 R.sup.6；R.sup.5和R.sup.6分别是氢或C.sub.1-6烷基，或者与它们连接的氮原子一起形成杂环环；R.sup.7是氢，C.sub.1-6烷氧基或C.sub.1-6烷基；或其盐。
• 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.

  替代4-氨基喹唑啉衍生物是胃酸分泌抑制剂。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