title: Synthesis and anti-human immunodeficiency virus type 1 (HIV-1) activity of 3-substituted derivatives of 3'-azido-3'-deoxythymidine (AZT), and inhibition of HIV-1 reverse transcriptase by their 5'-triphosphates.
abstract: Various 3-substituted 3'-azido-3'-deoxythymidine analogs (2a-i) were prepared by the reaction of 3'-azido-3'-deoxythymidine (1), AZT with N,N-dimethylformamide 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 microM. 3-Allyl-AZT 5'-triphosphate (9e), however, exhibited no inhibition of HIV-1 reverse transcriptase activity.
authors.affiliation: Department of Medicinal Chemistry, Gifu Pharmaceutical University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kitade
authors.forename: A
authors.initials: A
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Hirota
authors.forename: Y
authors.initials: Y
authors.lastname: Maki
authors.forename: H
authors.initials: H
authors.lastname: Nakane
authors.forename: K
authors.initials: K
authors.lastname: Ono
authors.forename: M
authors.initials: M
authors.lastname: Baba
authors.forename: S
authors.initials: S
authors.lastname: Shigeta
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D010710:Phosphates / Q000138:chemical synthesis / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors; D014764:Viral Proteins / Q000037:antagonists & inhibitors*; D015215:Zidovudine / Q000031:analogs & derivatives*
chemical_list: D000998:Antiviral Agents; D010710:Phosphates; D018894:Reverse Transcriptase Inhibitors; D014764:Viral Proteins; D015215:Zidovudine