碳环3'-氧杂-2',3'-双脱氧鸟苷及其7-脱氮鸟苷类似物的合成与抗病毒特性

Synthesis and antiviral properties of carbocyclic 3'-oxa-2',3'-dideoxyguanosine and its 7-deazaguanosine analogue.

作者信息

Chen X, Siddiqi S M, Schneller S W, Snoeck R, Balzarini J, De Clercq E

机构信息

Department of Chemistry, University of South Florida, Tampa 33620-5250.

出版信息

Antiviral Res. 1993 Apr;20(4):333-45. doi: 10.1016/0166-3542(93)90076-u.

DOI:10.1016/0166-3542(93)90076-u

PMID:8387261

Abstract

To evaluate analogues of the antiviral agent (R)-9-(3,4-dihydroxybutyl)guanine in which the side-chain C-3 hydroxyl oxygen is part of a five-membered ring, carbocyclic 3'-oxa-2',3'-dideoxyguanosine (4) and carbocyclic 3'-oxa-2',3'-dideoxy-7-deazaguanosine (5) have been synthesized in 17 and 14 steps, respectively, from 5-O-acetyl-1,2-O-isopropylidene-alpha-D-xylofuranose. Compounds 4 and 5 and their 6-chloro precursors were evaluated against a wide variety of DNA and RNA viruses. Only 4 showed any marginal activity and this was limited to HSV-1 and HSV-2. Even though 4 was less potent towards these latter two viruses than acyclovir, its mechanism and target of action is proposed to resemble that of acyclovir. The only toxicity observed for these compounds was observed in the cell growth assay with human embryonic lung cells.

摘要

为了评估抗病毒药物（R）-9-（3,4-二羟基丁基）鸟嘌呤的类似物，其中侧链C-3羟基氧是五元环的一部分，分别从5-O-乙酰基-1,2-O-异亚丙基-α-D-木糖呋喃糖经17步和14步合成了碳环3'-氧杂-2',3'-二脱氧鸟苷（4）和碳环3'-氧杂-2',3'-二脱氧-7-脱氮鸟苷（5）。对化合物4和5及其6-氯前体针对多种DNA和RNA病毒进行了评估。只有4显示出任何微弱的活性，且仅限于单纯疱疹病毒1型（HSV-1）和单纯疱疹病毒2型（HSV-2）。尽管4对后两种病毒的效力低于阿昔洛韦，但其作用机制和作用靶点被认为与阿昔洛韦相似。这些化合物观察到的唯一毒性出现在用人胚肺细胞进行的细胞生长试验中。