Abstract
Novel derivatives of 3-[[[2-(3, 4-dimethoxyphenyl)ethyl]carbamoyl]methyl]aminobenzamide (1) were synthesized in order to improve the solubility and bioavailability of the parent compound (1). Biopharmaceutical characteristics and antiulcer activity of the synthesized compounds were evaluated in rats. Three derivatives showed substantial improvement in aqueous solubilities. The absorption was also improved as determined by in situ loop method. Each of these three derivatives was administered orally to rats. The compound (4) and N-sulfomethyl derivative (5) were found to be more active in preventing stressinduced gastric ulcerration than the parent compound (1). Serum concentrations were also measured for each of these derivatives, but no significant improvement in bioavailability compared with compound (1) was observed. These results may implicate that the compounds (4) and (5) do not act as the prodrug of compound (1).
In conclusion, although no useful prodrug has been found, the novel compounds (4) and (5), which show antiulcer activity were discovered. The utility of these compounds as antiulcer agents is currently under investigation.
