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

Chem Pharm Bull (Tokyo). 1992 Jun;40(6):1470-5. doi: 10.1248/cpb.40.1470.

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-chlorobenza mide (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.

MeSH terms

  • Animals
  • Antiemetics / pharmacology
  • Benzamides / chemical synthesis
  • Benzamides / pharmacology*
  • Dopamine D2 Receptor Antagonists*
  • Gastric Emptying / drug effects*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Morpholines / chemical synthesis
  • Morpholines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship

Substances

  • Antiemetics
  • Benzamides
  • Dopamine D2 Receptor Antagonists
  • Morpholines
  • 4-amino-N-((4-benzyl-2-morpholinyl)methyl)-5-chloro-2-methoxybenzamide