Abstract: A new series of tricyclic derivatives were designed and synthesized on the basis of the structure of desloratadine.All the target compounds were identified by ¹H NMR and HR-MS.The H₁ receptor binding affinity experiment indicated that compound 7 was significantly more active than desloratadine.The in vitro histamine induced the contraction of guiea-pig ileum.Results showed that compound 7 had strong inhibitory activity on the ileum contraction.SAR study indicated that the calculated lgP values of compounds were consistent with their antihistamine activity.The binding mode of compound 7 and homology mode of H₁ receptor have been predicted by further molecular docking.