2-(N-acetylaminomethyl)-4-benzylmorpholine | 112913-96-9

• 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: 2-(N-acetylaminomethyl)-4-benzylmorpholine
• 英文别名: 2-<(acetylamino)methyl>-4-benzylmorpholine；2-(acetamidomethyl)-4-benzylmorpholine；2-acetylaminomethyl-4-benzylmorpholine；n-((4-Benzylmorpholin-2-yl)methyl)acetamide；N-[(4-benzylmorpholin-2-yl)methyl]acetamide
• CAS: 112913-96-9
• 化学式: C₁₄H₂₀N₂O₂
• mdl: MFCD12226014
• 分子量: 248.325
• InChiKey: JARCELFZNGRBJT-UHFFFAOYSA-N

物化性质

• 沸点：
  425.3±25.0 °C(Predicted)
• 密度：
  1.094±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  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 莫沙必利
  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 7.0h， 生成 2-(N-acetylaminomethyl)-4-benzylmorpholine
  参考文献：
  名称：

  Quinolone antimicrobial agents substituted with morpholines at the 7-position. Syntheses and structure-activity relationships

  摘要：

  A series of novel 7-substituted 1-cyclopropyl-6,8-difluoro- 1,4-dihydro-4-oxo-3-quinolinecarboxylic acids have been prepared and tested for antibacterial activities and for convulsive activities in combination with nonsteroidal antiinflammatory drug. Structure-activity relationships revealed that 7-(2-(aminomethyl)morpholino) derivative 28 had a better Gram-positive activity than the reference quinolones, such as ciprofloxacin, norfloxacin, and ofloxacin. Its Gram-negative activity was equipotent with those of norfloxacin and ofloxacin but was inferior to that of ciprofloxacin. In mouse systemic infection models, 28 showed an excellent therapeutic efficacy which might result from the potent antibacterial activity and suitable physicochemical properties. Convulsive activities of 7-morpholino derivatives in combination with nonsteroidal antiinflammatory drug fenbufen or its metabolite biphenylacetic acid markedly diminished as compared to those of 7-piperazino derivatives in the electrophysiological, biochemical, and behavioral experiments. These results suggest that 28 (Y-26611) is a novel quinolone with reduced neurotoxic excitatory adverse reaction.

  DOI：

  10.1021/jm00062a007

文献信息

• Novel benzamides as selective and potent gastric prokinetic agents. 1. Synthesis and structure-activity relationships of N-[(2-morpholinyl)alkyl]benzamides
  作者：Shiro Kato、Toshiya Morie、Katsuhiko Hino、Tatsuya Kon、Shunsuke Naruto、Naoyuki Yoshida、Tadahiko Karasawa、Junichi Matsumoto

  DOI：10.1021/jm00167a020

  日期：1990.5

  With the purpose of obtaining more potent and selective gastric prokinetic than metoclopramide (1), a new series of N-[(2-morpholinyl)alkyl]benzamides (17-52) were synthesized and their gastric prokinetic activity was evaluated by determining effects on the gastric emptying of phenol red semisolid meal and of resin pellets solid meal in rats and mice. The morpholinyl moiety was newly designed after

  为了获得比甲氧氯普胺（1）更有效和选择性的胃动力，合成了一系列新的N-[（2-吗啉基）烷基]苯甲酰胺（17-52），并通过测定对胃泌素的作用来评估其胃动力。大鼠和小鼠胃中酚红半固体粉和树脂颗粒固体粉的胃排空。考虑到西沙必利（2）的侧链结构后，新设计了吗啉基部分，并与甲氧氯普胺和西沙必利的4-氨基-5-氯-2-甲氧基苯甲酰基偶联时产生了所需的活性。苯甲酰基的取代基的改性显着影响了活性。特别是，
• 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。
• 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。
• Indolobenzazepine HCV NS5B inhibitors
  申请人：Bergstrom P. Carl

  公开号：US20070078122A1

  公开（公告）日：2007-04-05

  The invention encompasses compounds and salts of Formulas I, II, III, and IV as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.

  这项发明涵盖了Formula I、II、III和IV的化合物和盐，以及使用这些化合物的组合物和方法。这些化合物对丙型肝炎病毒（HCV）具有活性，并可用于治疗感染HCV的患者。
• AMIDE DERIVATIVE AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
  申请人：Kato Shiro

  公开号：US20100249399A1

  公开（公告）日：2010-09-30

  Disclosed is a compound having a strong affinity to serotonin-4 receptors, which is useful as an enterokinesis-promoting agent or a digestive tract function-improving agent. Specifically, disclosed is a compound represented by Formula (1) or a pharmaceutically acceptable salt thereof. Also specifically disclosed is a pharmaceutical composition containing a compound represented by Formula (1) or a pharmaceutically acceptable salt thereof. [In Formula (1), Ar represents a group represented by Formula (Ar-1) or Formula (Ar-2).]

  揭示了一种具有强烈亲和力的化合物，对5-羟色胺-4受体具有亲和力，可用作促进肠动力或改善消化道功能的药剂。具体地，揭示了一种由化学式（1）表示的化合物或其药学上可接受的盐。还具体揭示了一种含有由化学式（1）表示的化合物或其药学上可接受的盐的药物组合物。【在化学式（1）中，Ar代表由化学式（Ar-1）或化学式（Ar-2）表示的基团。】