Suicide Inhibitors of Reverse Transcriptase in the Therapy of AIDS and Other Retroviruses
Abstract
This project was designed to develop antiviral agents by adapting new enzymatic and pharmacokinetic principles to inhibition of the HIV-reverse transcriptase. Towards this end synthetic organic procedures were directed to synthesis of compounds in the following categories. 3' Nucleosidee spiroxiranes and a series of related compounds having the potential to function as suicide inhibitor of the reverse transcriptase through the 3' functionality; A series of sterol phosphonoformate analogs designed to improve delivery of the active phosphonoformate (PFA) moiety to sites of viral replication; and A series of 5' sterol ester derivatives of azido thymidine designed to improve the pharmacokinetics and blood half life of AZT. Synthetic compounds were tested for antiviral activity against HIV and EIAV in tissue culture, against purified HIV- reverse transcriptase in enzyme kinetic studies, where appropriate and samples of synthetic analogs were supplied to the US Army Antiviral Program for screening against a battery of 10 viruses of interest as military disease hazards.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1991
- Accession Number
- ADA241945
Entities
People
- Jennifer M. Bailey
Organizations
- George Washington University