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Updated: Aug 15, 2026

Rapid In Situ Hybridization using Oligonucleotide Probes on Paraformaldehyde-prefixed Brain of Rats with Serotonin Syndrome
Published on: September 23, 2015
Design and syntheses of a series of novel serotonin3 antagonists
1New Drug Research Laboratories, Kanebo Ltd., Osaka, Japan.
Abstract:
From a structural comparison study between serotonin and serotonin3 (5-HT3) antagonists using a two-dimensional grid template composed of regular hexagons, we deduced structural modification patterns from agonists to antagonists, and designed new 5-HT3 antagonist prototypes. Among them, 2-(4-methyl-1-piperazinyl)-1-butylbenzimidazole (6) was identified as a lead compound which has potent 5-HT3 antagonistic activity comparable to that of granisetron. Using a quantitative structure-activity relationships method, we optimized the structure of 6 and selected 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl)benzimidazole dimaleate (69, KB-6933), one of the most potent and long-acting 5-HT3 antagonists, as a candidate drug.
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