Synthsis and gastroprokinetic activity of N-(4-amino-5-chloro-2-methoxyphenyl)-4-benzyl-2-morpholineacetamide and related compounds

Article abstract of DOI:10.1016/0223-5234(96)88276-6

4-Amino-N-<(4-benzyl-2-morpholinyl)methyl>-5-chloro-2-methoxybenzamide 1a and its 2-ethoxy analogue 1b show a potent gastroprokinetic activity.To examine the effect of reversal of the amide linkage of 1a and 1b, N-(4-amino-5-chloro-2-methoxyphenyl)-4-benzyl-2-morpholineacetamide and related compounds (2 and 8-13) were prepared and evaluated for gastroprokinetic activity by determining their effects on gastric emptying of a phenol red semisolid meal a serotonin-4-receptor binding assay.Reversal of the amide bond resulted in a fall in activity; the amide bond of the 2-morpholinyl benzamides is essential for a potent gastroprokinetic activity.Molecular superimposition of 2c upon 1b using computer graphics suggested that the location of the morpholine ring and N-benzyl group is crucial for the activity. gastroprokinetic activity / 2-morpholineacetamide / molecular-superimposition / mosapride / 2-morpholinyl benzamide