Synthesis And Anti-human Immunodeficiency Virus Type 1 (hiv-1) Activity of 3-substituted Derivatives of 3 'x2018;-azido-3’-deoxythymidine (azt), And Inhibition of Hiv-1 Reverse Transcriptase By Their 5'-triphosphates” Riphosphates1

Abstract

Various 3-substituted 3 'x2018;-azido-3’-deoxythymidine 3 'x2018;-azido-3’-deoxythymidine analogs (2a—i) were prepared by the reaction of 3’- (1), AZT with N dialkylacetal or alkyl bromide in the presence of base and their activities against human-immunodeficiency virus type-1 (HIV-1) were evaluated. The corresponding 5’-triphosphate analogs (9) were also synthesized in order to examine inhibition of HIV-1 reverse transcriptase activity. Beyond expectation, some N3-derivatives of AZT were found to reserve the anti-HIV-1 activity to some extent. Among the compounds (2a—i) obtained, 3-allyl-AZT (2e) was the most active against HIV-1 replication in MT-4 cells in vitro with an EC50 value of 0.9 pm. 3-Allyl-AZT 5’-triphosphate (9e), however, exhibited no inhibition of HIV-1 reverse transcriptase activity. © 1992, The Pharmaceutical Society of Japan. All rights reserved.