【摘要】 目的设计合成一系列异核苷类似物及其双异丙基单磷酸酯并对其生物活性进行评价。方法采用传统加热法和微波辅助法选择性合成了一系列异核苷类似物及其双异丙基单磷酸酯,比较两种方法的不同,优化了微波反应条件,并考察了化合物细胞水平的抗H IV和抗HSV活性。结果在合成异核苷类似物及其双异丙基单磷酸酯化合物中,与传统加热法比较,微波辅助法在反应的选择性、转化率和收率上都有所提高。细胞水平活性评价试验结果表明,一些异核苷双异丙基单磷酸酯较其相应异核苷的抗HSV-2及H IV活性有较大程度提高。结论微波辅助法可应用于异核苷类似物及其双异丙基单磷酸酯的合成;细胞内激酶催化的核苷单磷酸化是其三磷酸化过程中的限速步骤,由于单磷酸酯化合物跨越了这一过程,抗病毒活性较相应核苷类似物有所提高。更多还原

【Abstract】 Although several isonuleoside triphosphates can be incorporated into the DNA chain and prolonged in various degrees,none of the corresponding nucleosides exhibited significant inhibitory potency against varies of virus in vitro.The active antiretroviral form of a nucleoside analog is its triphosphate anabolite.However,the monophosphorylation catalyzed by cellular kinases step is usually very restrictive.In order to bypass the first phosphorylation step,a series of isonuleoside analogues and their bis(isopropyl) monophosphates were designed and synthesized by selective microwave-aided method.The cell-based assay results showed that bis(isopropyl) isonucleoside monophosphates behaved improved potency against HSV-2 and HIV-1.更多还原