112887-45-3

Upstream product

• 112913-95-8 2-(N-acetylaminomethyl)morpholine 
• 112913-96-9 2-(N-acetylaminomethyl)-4-benzylmorpholine 
• 64473-35-4 3-(4-chlorophenyl)propyl bromide 
• 112887-55-5 2-acetylaminomethyl-4-[3-(4-chlorophenoxy)propyl]morpholine 

Downstream Products

• 112886-74-5 4-amino-5-chloro-N-[[4-[3-(4-chlorophenoxy)propyl]-2-morpholinyl]methyl]-2-methoxybenzamide 

Relevant academic research and scientific papers

Novel benzamides as selective and potent gastrokinetic agents. III. Synthesis and structure-activity relationships of 4-amino-5-chloro-2-methoxy- and 2-ethoxy-N-[(4-substituted 2-morpholinyl)methyl]-benzamides

A series of 4-amino-5-chloro-2-methoxy- and 2-ethoxy-N-[(4-substituted 2-morpholinyl)methyl]benzamides (11-44) were prepared and evaluated for gastrokinetic activity by determining their effects on the gastric emptying of phenol red semisolid meal in rats. The N-4 substituent includes alkyl, phenoxyalkyl, (4-fluorobenzoyl)alkyl, and heteroarylmethyl groups. The benzamide derivatives, having an isopropyl, isoamyl, neopentyl, 3-(4-chlorophenoxy)propyl, or pyridylmethyl group at N-4, showed potent in vivo gastric emptying activity. In particular, 4-amino-5-chloro-2-ethoxy-N-[[4-(3-pyridylmethyl)-2-morpholinyl]methyl ]benzamide (57b) was equipotent to the 4-fluorobenzyl analogue 1b (AS-4370 as its citrate) in the gastrokinetic activity on phenol red semisolid meal in rats and mice, and on resin pellet solid meal in rats. Moreover, compound 57b was free from dopamine D2 receptor antagonistic activity in both in vitro ([3H]spiperone binding) and in vivo (apomorphine-induced emesis in dogs) tests. Structure-activity relationships of compounds with various substituents at N-4 are also discussed.

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.