Stereoselective synthesis of desloratadine derivatives as antagonist of histamine

Abstract A series of desloratadine derivatives were stereoselectively synthesized and evaluated for H 1 antihistamine activity. For the evaluation of H 1 antihistamine activity, the in vitro histamine-induced contraction of the guinea-pig ileum assay (HC) was used. The synthesized desloratadine derivatives 7 , 8 and 9 are structurally related to rupatadine and were generated by replacement of the 5-methyl-3-pyridine group of rupatadine with γ-alkylidene butenolide. Their H 1 antihistamine activities have shown a high dependence on the exact nature of the substituent in the lactone ring. Optimum structures 7 , 8a and 8g display potent activity inhibiting histamine-induced effects.