偶联一氧化氮供体的槟榔碱结构类似物的合成及舒血管活性

Synthesis and vascular relaxing activity of arecoline derivatives coupled with nitric oxide donors

目的寻找作用于血管内皮、具有血管舒张作用的抗动脉粥样硬化药物。方法将N-甲基-1,2,3,6-四氢吡啶环通过酯键或酰胺键与NO供体单元3,4-二苯磺酰基-1,2,5-恶二唑-2-氧化物结合,合成具有NO释放和内皮乙酰胆碱靶标激动作用的槟榔碱结构类似物。结果合成了18个新的目标化合物,其结构经MS,IR,1HNMR及元素分析确证,并对合成的化合物进行大鼠胸主动脉血管舒张活性试验,所有化合物均具较好的体外舒血管活性。结论目标化合物具有较强的血管舒张作用,值得深入研究。

Aim To search for potential anti-atherosclerosis drugs with vascular relaxation activity, a series of agonists of endothelial targets were designed and synthesized. Methods Coupling 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. Results A 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. Conclusion This preliminary pharmacological tests showed that the candidates have good vasodilation activities and were worthy to be intensively studied.