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AIDS dementia: Synthesis and properties of a derivative of 3′‐azido‐3′‐deoxythymidine (AZT) that may become ‘locked’ in the central nervous system
Author(s) -
Torrence Paul F.,
Kinjo Jun-ei,
Lesiak Krystyna,
Balzarini Jan,
De Clercq Erik
Publication year - 1988
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(88)81319-x
Subject(s) - dementia , central nervous system , derivative (finance) , zidovudine , combinatorial chemistry , chemistry , human immunodeficiency virus (hiv) , pharmacology , neuroscience , medicine , biology , virology , business , viral disease , disease , finance
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.