Synthesis, biological evaluation and SAR studies of benzimidazole derivatives as H1-antihistamine agents

A series of benzimidazole derivatives have been designed, synthesized and evaluated for H1 antihistamine activity. Six compounds have showed potent antihistamine H1 activity. The primary SAR analysis indicated that benzyl or benzylidinyl substituted on the exo-nitrogen atom and C2 of the benzimidazole were significant. Further experiments indicated that compound 17d displayed excellent activity to reduce mast cell degranulation, moderate anti-PAF activity and decreased potency on hERG compared to astermizole. Hence compound 17d could serve as anti-allergic agent for further development.