Abstract: AimTo search for potential anti-atherosclerosis drugs with vascular relaxation activity, a series of agonists of endothelial targets were designed and synthesized. MethodsCoupling N-methyl-1,2,3,6-tetrahydrapyridine ring system with 3,4-dibenzenesulfonyl-1,2,5-oxadiazole-2-oxide through esterification or amidation, a series of arecoline derivatives containing NO donors were designed and synthesised. ResultsA novel series of compounds structurally related to arecoline have been prepared, the proposed structures of eighteen new compounds were established by IR, ¹H NMR, MS spectroscopy and elemental analysis. The effects of the target compounds on the vasodilation activity were tested in the isolated preparation of mice thoratic aorta. ConclusionThis preliminary pharmacological tests showed that the candidates have good vasodilation activities and were worthy to be intensively studied.