1-(8-Methoxy-4-phenylamino-quinolin-3-yl)-butan-1-one | 142781-74-6

• 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: 1-(8-Methoxy-4-phenylamino-quinolin-3-yl)-butan-1-one
• 英文别名: 1-(4-anilino-8-methoxyquinolin-3-yl)butan-1-one
• CAS: 142781-74-6
• 化学式: C₂₀H₂₀N₂O₂
• 分子量: 320.391
• InChiKey: DTZBHUMFEUZNDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  24
• 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：
  51.2
• 氢给体数：
  1
• 氢受体数：
  4

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 8.17h， 生成 1-(8-Methoxy-4-phenylamino-quinolin-3-yl)-butan-1-one
  参考文献：
  名称：

  Reversible inhibitors of the gastric (H+/K+)-ATPase. 3. 3-Substituted-4-(phenylamino)quinolines

  摘要：

  Previously, gastric (H+/K+)-ATPase inhibitors such as 2 have been prepared as analogues of 1a on the presumption that the 3-carbethoxy substituent plays a key role in establishing the orientation of the 4-arylamino group. In this paper we explore further the contribution made to activity by the quinoline 3-substituent. We show th bearing such a substituent, only a particular combination of properties provides high activity, both in as inhibitors of gastric acid secretion in vivo. The ability of the substituent to affect activity by restricting rotation about the C(quin)-N bond through a combination of both a pi-electron withdrawal and hydrogen bonding is supported by the current study. However, high activity is only achieved if the effect of this group on the quinoline pK(a) is kept to a minimum. 3-Acyl substituents provide an optimum combination of electronic properties. From this series, compound 17c (SK&F 96067) was shown to be a potent inhibitor of histamine-stimulated gastric acid secretion oral dosing in the Heidenhain pouch dog and was selected for further development and evaluation in man.

  DOI：

  10.1021/jm00096a018

文献信息

• Phosphorus mediated cyclisation of a β-arylaminoacrylamide to a quinoline: A simple synthesis of SK&F 96067
  作者：Ian P. Andrews、Robin Bannister、Steven K. Etridge、Norman J. Lewis、M. Valerie Mullane、Andrew S. Wells

  DOI：10.1016/0040-4039(95)01578-6

  日期：1995.10

  The reversible (H+/K+)ATPase inhibitor SK&F 96067 1 was prepared in two steps from Meldrum's Acid by cyclisation of the acrylamide 4 with Ph3P/C2Cl6/Et3N. Evidence for the formation of imidoylketene imine 3 was obtained by trapping with phenyl isocyanate. Thermal degradation of an amidine such as 12 also gave SK&F 96067 1.

  可逆（H + / K +）-ATP酶抑制剂SK＆F 96067 1在两个步骤中制备的由Meldrum酸由丙烯酰胺的环化4的Ph 3 P / C 2氯6 / ET 3 N.证据imidoylketene亚胺的形成3通过捕集异氰酸苯酯而获得。12的热降解（如12）也可得到SK＆F 96067 1。
• 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.