含噻二唑硫醚的槟榔碱新衍生物的合成及舒张血管活性  

Synthesis and Vascular Relaxing Activity of New Arecoline Analogues Containing Thiadiazole Sulfanylether

作　　者：杨锐生[1] 胡国强[1] 张忠泉[1] 黄文龙[2] 

机构地区：[1]河南大学药物研究所 [2]中国药科大学

出　　处：《应用化学》2007年第5期499-502,共4页Chinese Journal of Applied Chemistry

基　　金：国家自然科学基金(30070861);河南大学重点科研基金(04ZDZR009)资助项目

摘　　要：吡啶噻二唑硫醇经与卤化物缩合得吡啶噻二唑硫醚化合物4a～4e,碘甲烷季铵化得相应的吡啶盐5a～5e,用硼氢化钠还原吡啶盐,设计合成了出一系列在四氢吡啶环的3-位槟含有噻二唑硫醚基的榔碱衍生物6a～6e。化合物结构经元素分析、IR1、H NMR、MS测试技术确证。采用离体血管条法研究了目标化合物6a～6e体外舒张血管活性。结果表明,在10μmol/L浓度下,化合物6a、6b、6c、6d、6e对离体血管舒张率分别为22%、32%、40%、46%和8%,在相同的条件下,槟榔碱的舒张率为21%。The title compounds were designed and synthesized by condensation of the intermediate of pyridinyhhiadiazolyl-thiol 3 with various halides to pyridyl-substituted thiadiazole sulfanylethers（4a -4e）, followed by the quaternization of compounds 4a -4e with methyl iodide to afford the corresponding methylpyridiniun salts （5a - 5e）, and reduction of compounds 5a - e with sodium borohydride to give a series of the corresponding target compounds 6a - 6e containing the thiadiazole sulfanylether moiety at the 3-position of tetrahydropyridine ring. The structures of the synthesized compounds were characterized by IR, ^1H NMR, MS spectra and element analysis. The in vitro vascular relaxing activity of target compounds 6a - 6e were screened at the concentration 10 μmol/L, their vascular relaxing effects on isolated endothelial cells are 22%, 32%, 40%, 46% and 8% , respectively, while arecoline as reference drug was 21% at the same conditions.

关 键 词：槟榔碱衍生物 四氢吡啶 噻二唑 合成 舒张血管活性 

分 类 号：O621[理学—有机化学]