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Synthesis and anti-HIV activity of 2'-deoxy-2'-fluoro-4'-C-ethynyl nucleoside analogs.

Abstract：

:Based on the favorable antiviral profiles of 4'-substituted nucleosides, novel 1-(2'-deoxy-2'-fluoro-4'-C-ethynyl-beta-D-arabinofuranosyl)-uracil (1a), -thymine (1b), and -cytosine (2) analogs were synthesized. Compounds 1b and 2 exhibited potent anti-HIV-1 activity with IC(50) values of 86 and 1.34 nM, respectively, without significant cytotoxicity. Compound 2 was 35-fold more potent than AZT against wild-type virus, and also retained nanomolar antiviral activity against resistant strains, NL4-3 (K101E) and RTMDR. Thus, 2 merits further development as a novel NRTI drug.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Wang Q,Li Y,Song C,Qian K,Chen CH,Lee KH,Chang J

doi

10.1016/j.bmcl.2010.05.090

subject

Has Abstract

pub_date

2010-07-15 00:00:00

pages

4053-6

issue

14

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(10)00731-6

journal_volume

20

pub_type

杂志文章

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