2-(aminomethyl)-4-(ethoxycarbonyl)morpholine | 112914-11-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 2-(aminomethyl)-4-(ethoxycarbonyl)morpholine
• 英文别名: 2-Aminomethyl-4-ethoxycarbonylmorpholine；ethyl 2-(aminomethyl)morpholine-4-carboxylate
• CAS: 112914-11-1
• 化学式: C₈H₁₆N₂O₃
• 分子量: 188.227
• InChiKey: ZQZNIVUZKAVQAL-UHFFFAOYSA-N

物化性质

• 沸点：
  294.3±25.0 °C(Predicted)
• 密度：
  1.124±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  64.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(aminomethyl)-4-(ethoxycarbonyl)morpholine 在 氢氧化钾 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 、 丁酮 为溶剂， 反应 28.0h， 生成 4-amino-N-{[4-(4-carboxybenzyl)-2-morpholinyl]methyl}-5-chloro-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
• 作为产物：
  描述：

  2-[(4-苄基-2-吗啉基)甲基]-1H-异吲哚-1,3(2H)-二酮 在 一水合肼 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 1.17h， 生成 2-(aminomethyl)-4-(ethoxycarbonyl)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

• Substituted benzamide derivatives, for enhancing gastrointestinal
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US04870074A1

  公开（公告）日：1989-09-26

  Compounds of the formula: ##STR1## wherein R is hydrogen, alkoxycarbonyl, benzyloxycarbonyl, heteroarylalkyl, phenylalkenyl, or --T--(Y).sub.p --R.sub.6 (wherein T is single bond or alkylene, Y is oxygen, sulfur or carbonyl, R.sub.6 is phenyl, substituted phenyl, naphthyl, or diphenylmethyl, and p is 0 or 1, provided that when T is single bond, p is 0); R.sub.1 is halogen, hydroxy, alkoxy, cycloalkyloxy, alkenyloxy, alkynyloxy, alkoxy interrupted by oxygen or carbonyl, alkylthio, amino, monosubstituted amino, or a substituted alkoxy; R.sub.2 is hydrogen; R.sub.3 is hydrogen, halogen, amino, alkylamino, dialkylamino, alkanoylamino, or nitro; R.sub.4 is hydrogen, halogen, nitro, sulfamoyl, alkylsulfamoyl, or dialkylsulfamoyl; or any two adjacent groups of the R.sub.1, R.sub.2, R.sub.3 and R.sub.4 may combine to form alkylenedioxy, and the remaining two groups are each hydrogen; R.sub.5 is hydrogen or alkyl; X is alkylene; m and n are each 1 or 2; provided that at least one of the groups R.sub.2, R.sub.3 and R.sub.4 is other than hydrogen, and acid addition salts, quaternary ammonium salts and N-oxide derivatives thereof, processes for preparation thereof, and pharmaceutical composition containing the same. Said compounds, salts and N-oxide derivatives thereof show excellent gastrointestinal motility enhancing activity.

  式中R为氢、烷氧羰基、苄氧羰基、杂环烷基、苯基烯基，或--T--(Y).sub.p --R.sub.6（其中T为单键或烷基，Y为氧、硫或羰基，R.sub.6为苯基、取代苯基、萘基或二苯甲基，p为0或1，但当T为单键时，p为0）；R.sub.1为卤素、羟基、烷氧基、环烷氧基、烯基氧基、炔基氧基、被氧或羰基中断的烷氧基、烷基硫醚、氨基、单取代氨基，或取代烷氧基；R.sub.2为氢；R.sub.3为氢、卤素、氨基、烷基氨基、二烷基氨基、烷酰氨基，或硝基；R.sub.4为氢、卤素、硝基、磺酰胺基、烷基磺酰胺基，或二烷基磺酰胺基；或R.sub.1、R.sub.2、R.sub.3和R.sub.4中的任意两个相邻基团可结合形成亚烷二氧基，其余两个基团各为氢；R.sub.5为氢或烷基；X为烷基；m和n各为1或2；但R.sub.2、R.sub.3和R.sub.4中至少有一个基团不是氢，以及其酸盐、季铵盐和N-氧化物衍生物，其制备方法，以及含有它们的药物组合物。所述化合物、盐及其N-氧化物衍生物表现出优异的胃肠动力增强活性。
• TRIFLUOROMETHYL-SUBSTITUTED SULFONAMIDE AS BCL-2-SELECTIVE INHIBITOR
  申请人：Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

  公开号：EP3858832A1

  公开（公告）日：2021-08-04

  Disclosed is a trifluoromethyl-substituted sulfonamide BCL-2-selective inhibitor, in particular disclosed are a compound of formula I, a stereoisomer or a pharmaceutically acceptable salt thereof, a preparation method therefor, and a pharmaceutical composition thereof. Also disclosed are the uses of said compound and of a pharmaceutical composition comprising same for treating anti-apoptotic BCL-2-related diseases, such as cancer.

  公开了一种三氟甲基取代的磺酰胺类 BCL-2 选择性抑制剂，特别是公开了一种式 I 的化合物、其立体异构体或药学上可接受的盐、其制备方法及其药物组合物。还公开了所述化合物及其药物组合物治疗抗凋亡 BCL-2 相关疾病（如癌症）的用途。
• EP3858832
  申请人：——

  公开号：——

  公开（公告）日：——
• Substituted benzamide derivatives, processes for the preparation thereof, and pharmaceutical compositions containing the same
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：EP0243959B1

  公开（公告）日：1992-08-19
• KON, TATSUYA;KATO, SHIRO;MORIE, TOSHIYA;OHNO, KAZUNORI;HINO, KATSUHIKO;KA+
  作者：KON, TATSUYA、KATO, SHIRO、MORIE, TOSHIYA、OHNO, KAZUNORI、HINO, KATSUHIKO、KA+

  DOI：——

  日期：——