4-amino-5-chloro-N-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-2-methoxybenzamide | 112885-13-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-amino-5-chloro-N-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-2-methoxybenzamide
• CAS: 112885-13-9
• 化学式: C₂₀H₂₂Cl₃N₃O₃
• 分子量: 458.772
• InChiKey: WIQMTTSBXAWCHL-UHFFFAOYSA-N

物化性质

• 熔点：
  89-91 °C(Solv: ethanol (64-17-5))
• 沸点：
  579.5±50.0 °C(Predicted)
• 密度：
  1.370±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  76.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(N-acetylaminomethyl)-4-benzylmorpholine 在 palladium on activated charcoal 盐酸 、 氢气 、 potassium carbonate 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium iodide 作用下， 以 乙醇 、 二氯甲烷 、 丁酮 为溶剂， 反应 25.0h， 生成 4-amino-5-chloro-N-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-2-methoxybenzamide
  参考文献：
  名称：

  Novel benzamides as selective and potent gastrokinetic agents. 2. Synthesis and structure-activity relationships of 4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl]benzamide citrate (AS-4370) and related compounds

  摘要：

  The title compounds (19-55) with a 4-substituted 2-(aminomethyl) morpholine group were prepared and evaluated for the gastrokinetic activity by determining their effect on gastric emptying of phenol red semisolid meal in rats. Introduction of chloro, fluoro, and trifluoromethyl groups to the benzyl group of the parent compounds 1a and 1b enhanced the activity. Among compounds tested, 4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]?? methyl]benzamide (23b) showed the most potent gastic emptying activity (effects on phenol red semisolid meal in rats and mice, and on resin pellets solid meal in rats). The gastrokinetic activity of 23b citrate (AS-4370) compared very favorably with that of cisapride and was higher than that of metoclopramide. In contrast to metoclopramide and cisapride, AS-4370 was free from dopamine D2 receptor antagonistic activity in both in vitro ([H-3]spiperone binding) and in vivo (apomorphine-induced emesis in dogs) tests.

  DOI：

  10.1021/jm00106a023

文献信息

• KATO, SHIRO;MORIE, TOSHIYA;KON, TATSUYA;YOSHIDA, NAOYUKI;KARASAWA, TADAHI+, J. MED. CHEM., 34,(1991) N, C. 616-624
  作者：KATO, SHIRO、MORIE, TOSHIYA、KON, TATSUYA、YOSHIDA, NAOYUKI、KARASAWA, TADAHI+

  DOI：——

  日期：——
• Novel benzamides as selective and potent gastrokinetic agents. 2. Synthesis and structure-activity relationships of 4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl]benzamide citrate (AS-4370) and related compounds
  作者：Shiro Kato、Toshiya Morie、Tatsuya Kon、Naoyuki Yoshida、Tadahiko Karasawa、Junichi Matsumoto

  DOI：10.1021/jm00106a023

  日期：1991.2

  The title compounds (19-55) with a 4-substituted 2-(aminomethyl) morpholine group were prepared and evaluated for the gastrokinetic activity by determining their effect on gastric emptying of phenol red semisolid meal in rats. Introduction of chloro, fluoro, and trifluoromethyl groups to the benzyl group of the parent compounds 1a and 1b enhanced the activity. Among compounds tested, 4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]?? methyl]benzamide (23b) showed the most potent gastic emptying activity (effects on phenol red semisolid meal in rats and mice, and on resin pellets solid meal in rats). The gastrokinetic activity of 23b citrate (AS-4370) compared very favorably with that of cisapride and was higher than that of metoclopramide. In contrast to metoclopramide and cisapride, AS-4370 was free from dopamine D2 receptor antagonistic activity in both in vitro ([H-3]spiperone binding) and in vivo (apomorphine-induced emesis in dogs) tests.