112885-32-2

Upstream product

• 131322-23-1 <2-(acetylamino)methyl>morpholine acetyl salt 
• 112913-96-9 2-(N-acetylaminomethyl)-4-benzylmorpholine 
• 7206-70-4 4-amino-5-chloro-2-methoxybenzoic acid 
• 112914-10-0 4-(2-Aminomethyl-morpholin-4-ylmethyl)-benzonitrile 

Relevant academic research and scientific papers

Novel benzamides as selective and potent gastrokinetic agents. 2.1 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

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 gastric 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 ([3H]spiperone binding) and in vivo (apomorphine-induced emesis in dogs) tests.

Substituted benzamide derivatives, for enhancing gastrointestinal motility

Compounds of the formula: STR1 wherein R is hydrogen, alkoxycarbonyl, benzyloxycarbonyl, heteroarylalkyl, phenylalkenyl, or --T--(Y)p --R6 (wherein T is single bond or alkylene, Y is oxygen, sulfur or carbonyl, R6 is phenyl, substituted phenyl, naphthyl, or diphenylmethyl, and p is 0 or 1, provided that when T is single bond, p is 0); R1 is halogen, hydroxy, alkoxy, cycloalkyloxy, alkenyloxy, alkynyloxy, alkoxy interrupted by oxygen or carbonyl, alkylthio, amino, monosubstituted amino, or a substituted alkoxy; R2 is hydrogen; R3 is hydrogen, halogen, amino, alkylamino, dialkylamino, alkanoylamino, or nitro; R4 is hydrogen, halogen, nitro, sulfamoyl, alkylsulfamoyl, or dialkylsulfamoyl; or any two adjacent groups of the R1, R2, R3 and R4 may combine to form alkylenedioxy, and the remaining two groups are each hydrogen; R5 is hydrogen or alkyl; X is alkylene; m and n are each 1 or 2; provided that at least one of the groups R2, R3 and R4 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.