Novel benzimidazole-4-carboxylic acid derivatives as potent and selective 5-HT3 receptor ligands

A series of benzimidazole-4-carboxylic acid derivatives was synthesized and evaluated for affinity at 5-HT3 and 5-HT4 serotoninergic receptors. Compounds 1b, c and j exhibited high affinity for the 5-HT3 receptors (Ki=6.1, 3.7 and 4.9 nM, respectively) and no significant affinity for 5-HT4 (Ki>1000 nM) and 5-HT1A (Ki>10 000 nM) sites. Preliminary studies showed that 1c displayed activity in the two-compartment behavioural model.