Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
Novel Benzamides as Selective and Potent Gastrokinetic Agents. IV. Synthesis and Structure-Activity Relationships of 2-Substituted 4-Amino-N-[(4-benzyl-2-morpholinyl)methyl]-5-chlorobenzamides
Shiro KATOToshiya MORIENaoyuki YOSHIDAJun-ichi MATSUMOTO
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Volume 40 (1992) Issue 6 Pages 1470-1475

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Abstract

A new series of 2-substituted 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-5-chlorobenzamides (4-39) including a few 4-fluorobenzyl analogues were prepared and evaluated for their gastrokinetic activity by determining their effects on the gastric emptying activity of phenol red semisolid meal in rats. The C-2 substituent comprises alkoxy and variously substituted alkoxy groups. Among the derivatives, 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-2-(n-butoxy)-5-chlorobenzamide (5), its 4-fluorobenzyl (6), and 3-methyl-2-butenyloxy analogues (22) were superior to cisapride and essentially equipotent to the 2-ethoxy analogue (1b, AS-4370 as its citrate) in gastrokinetic activity. These compounds, like AS-4370, had no dopamine D2 receptor antagonistic activity.

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