Synthesis and SAR studies of benzimidazolone derivatives as histamine H3-receptor antagonists

A novel series of benzimidazolone-containing histamine H₃-receptor antagonists were prepared and their structure–activity relationship was explored. These benzimidazolone analogs demonstrate potent H₃-receptor binding affinities, no P450 enzyme inhibition, and strong H₃ functional activity. Compound 1o exhibits the best overall profile with H₃K_i = 0.95 nM and rat AUC = 12.9 μM h.