Synthesis and anti-HIV activity of 2'-deoxy-2'-fluoro-4'-C-ethynyl nucleoside analogs.
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.
Wang
Qiang
Q
Department of Chemistry, Zhengzhou University, PR China.
Li
Yanfeng
Y
Song
Chuanjun
C
Qian
Keduo
K
Chen
Chin-Ho
CH
Lee
Kuo-Hsiung
KH
Chang
Junbiao
J
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D003853:Deoxyribonucleosides / Q000138:chemical synthesis* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D003853:Deoxyribonucleosides