新型AMD治疗剂的合成及生物活性研究

 目的研发一种通过增加一氧化氮(NO)释放从而选择性改善脉络膜血流的新型药物,用于治疗年龄相关性黄斑变性(AMD)。方法以3,4,5-三甲氧基苯甲醛为原料,经7步反应制得一对立体异构体ZX-4及ZX-5,波谱及元素分析确证其结构,并测定它们对NO生成及眼组织血流的影响。结果以高收率获得了目标化合物,发现反式异构体ZX-5能促进细胞NO的释放,选择性增加脉络膜血流,而顺式异构体ZX-4无此药理作用。结论ZX-5有可能用于AMD的预防或治疗。

Studies on Synthesis and Biological Activity of Novel Anti-AMD Agent

OBJECTIVE To synthesize a compound, which can specifically facilitate choroidal blood flow via increasing of nitric oxide(NO), for the treatment of age-related macular degeneration(AMD). METHODS A pair of stereoisomers was prepared by seven steps from 3,4,5-trimethoxybenzaldehyde and their structures were confirmed by IR,~ 1 H-NMR,MS and elemental analysis. The production of nitric oxide in vitro and the blood flow of rabbit eye tissue were investigated. RESULTS The target compounds were prepared in high yields. Trans isomer ZX-5 released significant amount of NO and specifically increased the choroidal blood flow,while cis isomer ZX-4 did not show these activities.CONCLUSION ZX-5 is a promising compound in the prevention/treatment of AMD in the elder.