A new 5-HT3 receptor ligand. II. Structure-activity analysis of 5-HT3 receptor agonist action in the gut

Article abstract of DOI:10.1248/cpb.46.445

Several modified 2-piperazinyl benzoxazole derivatives, which exhibit an agonistic effect on gastrointestinal motility, were synthesized and their effects on the contraction of guinea-pig ileum were examined. The quaternary piperazinyl benzoxazole structure has a restricted conformation and stereostructure compared to those of the other 5-HT₃ receptor agonists, serotonin and meta-chlorophenylbiguanide. The mutual positions of the aromatic ring, nitrogen atom and terminal amine are considered to form the pharmacophore of the 5-HT₃ receptor agonist in the gut. In the serotonin- evoked reflex bradycardia [Bezold-Jarisch (B-J) reflex] inhibition test using rats the B-J reflex-inducing ratio was different for each synthesized compound. These results suggest that, in these 5-HT₃ receptor agonists, the substituents of the benzoxazole ring influence the B-J reflex-inducing activity in rats.

Full text of DOI:10.1248/cpb.46.445

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