methyl 3-butyryl-4(1H)-quinolone-8-carboxylate | 126495-79-2

• 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: methyl 3-butyryl-4(1H)-quinolone-8-carboxylate
• 英文别名: methyl 3-butanoyl-4-oxo-1H-quinoline-8-carboxylate
• CAS: 126495-79-2
• 化学式: C₁₅H₁₅NO₄
• 分子量: 273.288
• InChiKey: JCFGEJOXTYQUMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  72.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-butyryl-4(1H)-quinolone-8-carboxylate 在 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.5h， 生成 methyl 3-butyryl-4-(2-methylphenyl-amino)-quinoline-8-carboxylate
  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， 以 二苯醚 为溶剂， 反应 1.33h， 生成 methyl 3-butyryl-4(1H)-quinolone-8-carboxylate
  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
• 作为试剂：
  描述：

  2-((Z)-2-Ethoxycarbonyl-3-oxo-hex-1-enylamino)-benzoic acid methyl ester 在 methyl 3-butyryl-4(1H)-quinolone-8-carboxylate 、 乙醚 作用下， 以 二苯醚 为溶剂， 反应 1.0h， 生成 methyl 3-butyryl-4(1H)-quinolone-8-carboxylate
  参考文献：
  名称：

  Substituted 4-aminoquinoline derivatives as gastric acid secretion

  摘要：

  该公式代表的是4-氨基喹唑啉衍生物的替代物，其中R1为氢，C1-6烷基，C1-6烷氧基，C1-6烷氧基C1-6烷基，C3-6环烷基，C3-6环烷基C1-6烷基，苯基C1-6烷基，苯基可以选择性地被取代；R2为氢，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，C1-6酰基或三氟甲基；m为1至3；p为0至4；R3为COR4；R4为羟基，C1-6烷氧基或NR5R6；R5和R6分别为氢或C1-6烷基，或与它们所连接的氮原子一起形成杂环环；R7为氢，C1-6烷氧基或C1-6烷基；或其盐。

  公开号：

  US05089498A1

文献信息

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

  公开号：EP0339768A1

  公开（公告）日：1989-11-02

  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 C₁₋₆alkylthio, halogen, cyano, hydroxy, carbamoyl, carboxy, C₁₋₆alkanoyl or trifluoromethyl; m is 1 to 3; p is 0 to 4; R³ is COR⁴; R⁴ is hydroxy, C₁₋₆alkoxy or NR⁵R⁶; R⁵ and R⁶ are each hydrogen or C₁₋₆alkyl or together with the nitrogen atom to which they are attached form a heterocyclic ring; and R⁷ is hydrogen, hydroxy, C₁₋₆alkoxy or C₁₋₆alkyl, processes for preparing them, intermediates useful in their preparation, pharmaceutical compositions containing them and their use in therapy as inhibitors for gastric acid secretions.

  结构(I)的化合物： 其中 R¹ 是氢、C₁₋₆烷基、C₁₋₆烷氧基、C₁₋₆-C₁₋₆-烷基、C₃₋₆环烷基、C₃₋₆环烷基、苯基、苯基，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、C₁₋₆烷酰基或三氟甲基；m 是 1 至 3；p 是 0 至 4；R³ 是 COR⁴；R⁴ 是羟基、C₁₋₆ 烷氧基或 NR⁵R⁶；R⁵ 和 R⁶ 各自是氢或 C₁₋₆ 烷基，或与所连接的氮原子一起形成杂环；R⁷是氢、羟基、C₁₋₆烷氧基或 C₁₋₆烷基，制备它们的工艺，用于制备它们的中间体，含有它们的药物组合物，以及它们在治疗中作为胃酸分泌抑制剂的用途。
• US5089498A
  申请人：——

  公开号：US5089498A

  公开（公告）日：1992-02-18
• 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.
• Substituted 4-aminoquinoline derivatives as gastric acid secretion
  申请人：SmithKline Beckman Intercredit B.V.

  公开号：US05089498A1

  公开（公告）日：1992-02-18

  Substituted 4-aminiquinazoline derivatives of the formula: ##STR1## in which R.sup.1 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 trifluromethyl; 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：## STR1 ## 中的4-氨基喹唑啉衍生物的替代物：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，苯基可以选择性地被取代；R.sup.2为氢，C.sub.1-6烷基，C.sub.1-6烷氧基，氨基，C.sub.1-6烷基硫醚，卤素，氰基，羟基，氨基甲酰基，羧基，C.sub.1-6酰基或三氟甲基；m为1至3；p为0至4；R.sup.3为COR.sup.4；R.sup.4为羟基，C.sub.1-6烷氧基或NR.sup.5R.sup.6；R.sup.5和R.sup.6分别为氢或C.sub.1-6烷基，或与它们连接的氮原子一起形成一个杂环环； R.sup.7为氢，C.sub.1-6烷氧基或C.sub.1-6烷基；或其盐。