新型2'-氟-3'-羟甲基-5'-脱氧苏糖基膦酸核苷类似物作为抗病毒药物的合成
Synthesis of novel 2'-fluoro-3'-hydroxymethyl-5'-deoxythreosyl phosphonic acid nucleoside analogues as antiviral agents.
作者信息
Kim Kyung Mi, Hong Joon Hee
机构信息
a BK-21 Project Team, College of Pharmacy Chosun University , Kwangju , Republic of Korea.
出版信息
Nucleosides Nucleotides Nucleic Acids. 2014;33(2):92-109. doi: 10.1080/15257770.2013.874561.
A series of purine 5'-deoxyphosphonate analogues were designed and synthesized to mimic naturally occurring purine monophosphate from 1,3-dihydroxyacetone as starting material. The discovery of threosyl phosphonate nucleoside (PMDTA, EC50 = 2.53 μM) as a potent anti-HIV agent has led to the synthesis and biological evaluation of 2',3'-modified 5'-deoxyversions of the threosyl phosphonate nucleosides. The synthesized 2'-fluoro-3'-hydroxymethyl 5'-deoxythreosyl phosphonic acid nucleoside analogues 14, 18, 23, and 27 were tested for anti-HIV activity as well as cytotoxicity. The adenine analogue 18 exhibits weak in vitro anti-HIV-1 activity (EC50 = 19.2 μM).
以1,3 - 二羟基丙酮为起始原料，设计并合成了一系列嘌呤5'-脱氧膦酸酯类似物，以模拟天然存在的嘌呤单磷酸。苏糖基膦酸酯核苷（PMDTA，EC50 = 2.53 μM）作为一种有效的抗HIV药物的发现，促使了苏糖基膦酸酯核苷的2',3'-修饰5'-脱氧类似物的合成和生物学评价。对合成的2'-氟-3'-羟甲基5'-脱氧苏糖基膦酸核苷类似物14、18、23和27进行了抗HIV活性和细胞毒性测试。腺嘌呤类似物18表现出较弱的体外抗HIV-1活性（EC50 = 19.2 μM）。
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