title: Synthesis and anti-HIV properties of new carbamate prodrugs of AZT.
abstract: A series of new 5'-O-carbamate prodrugs of AZT have been prepared. The stability in biological media, anti-HIV properties and pharmacokinetic parameters in dogs were evaluated. The compounds display moderate anti-HIV activity in cell culture. After oral administration of carbamate IV in dogs, both intact prodrug IV and released AZT were discovered in dog blood. Pharmacokinetic parameters of the compound IV were estimated. Half-life (T(1/2)) of AZT released after oral administration of IV in dogs was close to that after administration of AZT itself, and time to the maximum concentration (T(max)) of AZT released from IV was two and three times longer compared with that of AZT and H-phosphonate AZT, respectively. Acute toxicity was more than five times less if compared with AZT. As a result, we consider this series of carbamate derivatives of AZT as perspective for development of anti-HIV agents.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov St., Moscow 119991, Russia.
authors.forename: Pavel N
authors.initials: PN
authors.lastname: Solyev
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Shipitsin
authors.forename: Inna L
authors.initials: IL
authors.lastname: Karpenko
authors.forename: Dmitry N
authors.initials: DN
authors.lastname: Nosik
authors.forename: Ludmila B
authors.initials: LB
authors.lastname: Kalnina
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Kochetkov
authors.forename: Marina K
authors.initials: MK
authors.lastname: Kukhanova
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Jasko
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity; D002219:Carbamates / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D006207:Half-Life; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity; D015215:Zidovudine / Q000737:chemistry*
chemical_list: D019380:Anti-HIV Agents; D002219:Carbamates; D011355:Prodrugs; D015215:Zidovudine