AIDS dementia: Synthesis and properties of a derivative of 3′‐azido‐3′‐deoxythymidine (AZT) that may become ‘locked’ in the central nervous system

FEBS Letters

De Clercq, Erik²  Lesiak, Krystyna¹  Kinjo, Jun-ei¹  Balzarini, Jan²  Torrence, Paul F.¹ 

[1] Section on Biomedical Chemistry, Laboratory of Analytical Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA;Rega Institute, Catholic University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium

关键词: HIV-1;    Antiviral activity;    Anti-retrovirus agent;    Nucleoside;    (Rat brain);   

DOI  :  10.1016/0014-5793(88)81319-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In an attempt to provide a derivative of 3′-azido-3′-deoxythymidine (AZT) which might be sequestered in the central nervous system and release AZT, the dihydropyridine ester 5′-(1,4-dihydro-1-methyl-3-pyridinylcarbonyl)-3′-deoxythymidine, was synthesized in a three step sequence. This material showed potent anti-HIV-1 activity in MT-4 cells most probably by hydrolysis to the parent nucleoside, AZT. This dihydropyridine derivative of AZT could be easily oxidized to a positively charged pyridinium derivative of AZT in rat brain cytosol. In turn the pyridinium form could be hydrolyzed, non-enzymatically, to AZT.

【 授权许可】

Unknown