2-(N-acetylaminomethyl)-4-(p-trifluoromethylbenzyl)morpholine | 112887-03-3

• 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: 2-(N-acetylaminomethyl)-4-(p-trifluoromethylbenzyl)morpholine
• 英文别名: N-[[4-[[4-(trifluoromethyl)phenyl]methyl]morpholin-2-yl]methyl]acetamide
• CAS: 112887-03-3
• 化学式: C₁₅H₁₉F₃N₂O₂
• 分子量: 316.323
• InChiKey: YSZPEHKIRORZHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(N-acetylaminomethyl)-4-(p-trifluoromethylbenzyl)morpholine 在 sodium hydroxide 作用下， 以 盐酸 为溶剂， 生成 2-aminomethyl-4-(p-trifluoromethylbenzyl)morpholine
  参考文献：
  名称：

  Pyrimidine derivatives

  摘要：

  嘧啶衍生物可用作胃肠促动力药物，其化学式表示为##STR1##其中X为O或NR.sup.5，Y为O、S或NR.sup.5，其中R.sup.5为氢原子、C.sub.1 -C.sub.6烷基或类似物；R.sup.1和R.sup.2可以相同也可以不同，每个都是氢原子、C.sub.1 -C.sub.6烷基或类似物；R.sup.3为CN，或COOR.sup.6，其中R.sup.6为C.sub.1 -C.sub.6烷基、C.sub.3 -C.sub.6环烷基、芳基或类似物；R.sup.4为--SR.sup.7或--NR.sup.8 R.sup.9，其中R.sup.7为C.sub.1 -C.sub.6烷基；R.sup.8为C.sub.1 -C.sub.6烷基或类似物；R.sup.9为氢原子、C.sub.1 -C.sub.6烷基或类似物，或R.sup.8和R.sup.9可以与它们连接的氮原子一起表示为化学式(X)的N-取代哌嗪环，其中R.sup.10代表C.sub.1 -C.sub.6烷基或类似物，或其药理学上可接受的盐。上述化合物可用作治疗消化道疾病的胃肠促动力药物。

  公开号：

  US05736550A1
• 作为产物：
  描述：

  2-(N-acetylaminomethyl)-4-benzylmorpholine 在 palladium on activated charcoal 氢气 、 potassium carbonate 、 溶剂黄146 、 potassium iodide 作用下， 以 乙醇 、 丁酮 为溶剂， 反应 17.0h， 生成 2-(N-acetylaminomethyl)-4-(p-trifluoromethylbenzyl)morpholine
  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

• Pyrimidine derivatives
  申请人：Nisshin Flour Milling Co., Ltd.

  公开号：US05736550A1

  公开（公告）日：1998-04-07

  Pyrimidine derivatives useful as a gastrointestinal prokinetic agent, represented by formula ##STR1## wherein X is O or NR.sup.5, Y is O, S or NR.sup.5 wherein R.sup.5 is a hydrogen atom, a C.sub.1 -C.sub.6 alkyl group or the like; R.sup.1 and R.sup.2 may be the same or different and each is a hydrogen atom, a C.sub.1 -C.sub.6 alkyl group or the like; R.sup.3 is CN, or COOR.sup.6 wherein R.sup.6 is a C.sub.1 -C.sub.6 alkyl group, a C.sub.3 -C.sub.6 cycloalkyl group, an aryl group or the like; R.sup.4 is --SR.sup.7 or --NR.sup.8 R.sup.9 wherein R.sup.7 is a C.sub.1 -C.sub.6 alkyl group; R.sup.8 is a C.sub.1 -C.sub.6 alkyl group or the like; R.sup.9 is a hydrogen atom, a C.sub.1 -C.sub.6 alkyl group or the like, or R.sup.8 and R.sup.9 may represent, together with the nitrogen atom to which they are attached, an N-substituted piperazine ring of formula (X) ##STR2## wherein R.sup.10 represents a C.sub.1 -C.sub.6 alkyl group or the like or a pharmacologically acceptable salt thereof. The above-mentioned compounds are useful as a gastrointestinal prokinetic agent used for the therapy of digestive tract diseases.

  嘧啶衍生物可用作胃肠促动力药物，其化学式表示为##STR1##其中X为O或NR.sup.5，Y为O、S或NR.sup.5，其中R.sup.5为氢原子、C.sub.1 -C.sub.6烷基或类似物；R.sup.1和R.sup.2可以相同也可以不同，每个都是氢原子、C.sub.1 -C.sub.6烷基或类似物；R.sup.3为CN，或COOR.sup.6，其中R.sup.6为C.sub.1 -C.sub.6烷基、C.sub.3 -C.sub.6环烷基、芳基或类似物；R.sup.4为--SR.sup.7或--NR.sup.8 R.sup.9，其中R.sup.7为C.sub.1 -C.sub.6烷基；R.sup.8为C.sub.1 -C.sub.6烷基或类似物；R.sup.9为氢原子、C.sub.1 -C.sub.6烷基或类似物，或R.sup.8和R.sup.9可以与它们连接的氮原子一起表示为化学式(X)的N-取代哌嗪环，其中R.sup.10代表C.sub.1 -C.sub.6烷基或类似物，或其药理学上可接受的盐。上述化合物可用作治疗消化道疾病的胃肠促动力药物。
• NOVEL PYRIMIDINE DERIVATIVE
  申请人：NISSHIN FLOUR MILLING CO., LTD.

  公开号：EP0760368A1

  公开（公告）日：1997-03-05

  Pyrimidine derivatives useful as a gastrointestinal prokinetic agent, represented by formula (I) wherein X is O or NR5, Y is O, S or NR5 wherein R5 is a hydrogen atom, a C1-C6 alkyl group or the like; R1 and R2 may be the same or different and each is a hydrogen atom, a C1-C6 alkyl group or the like; R3 is CN, or COOR6 wherein R6 is a C1-C6 alkyl group, a C3-C6 cycloalkyl group, an aryl group or the like; R4 is -SR7 or -NR8R9 wherein R7 is a C1-C6 alkyl group; R8 is a C1-C6 alkyl group or the like; R9 is a hydrogen atom, a C1-C6 alkyl group or the like, or R8 and R9 may represent, together with the nitrogen atom to which they are attached, an N-substituted piperazine ring of formula (X) wherein R10 represents a C1-C6 alkyl group or the like or a pharmacologically acceptable salt thereof. The above-mentioned compounds are useful as a gastrointestinal prokinetic agent used for the therapy of digestive tract diseases.

  可用作胃肠促动力药的嘧啶衍生物，由式（I）表示 其中 X 是 O 或 NR5，Y 是 O、S 或 NR5，其中 R5 是氢原子、C1-C6 烷基或类似物； R1 和 R2 可以相同或不同，各自为氢原子、C1-C6 烷基或类似物； R3 是 CN 或 COOR6，其中 R6 是 C1-C6 烷基、C3-C6 环烷基、芳基或类似基团； R4 是-SR7 或-NR8R9，其中 R7 是 C1-C6 烷基； R8 是 C1-C6 烷基或类似基团； R9是氢原子、C1-C6烷基或类似基团，或R8和R9可与它们所连接的氮原子一起代表式(X)的N-取代的哌嗪环 其中 R10 代表 C1-C6 烷基或类似基团或其药理学上可接受的盐。 上述化合物可用作治疗消化道疾病的胃肠促动力药。
• PYRIMIDINE DERIVATIVES
  申请人：NISSHIN FLOUR MILLING CO., LTD.

  公开号：EP0760368B1

  公开（公告）日：1999-07-28
• US5736550A
  申请人：——

  公开号：US5736550A

  公开（公告）日：1998-04-07
• 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.