3'-Substituted 2',3'-dideoxynucleoside analogs as potential anti-HIV (HTLV-III/LAV) agents
- 31 July 1987
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 30 (8), 1270-1278
- https://doi.org/10.1021/jm00391a003
Abstract
A series of 2'',3''-unsaturated and 3''-substituted 2'',3''-dideoxynucleoside analogues of purines and pyrimidines have been synthesized and evaluated for their inhibitory activity against human immunodeficiency virus (HIV). The 2'',3''-unsaturated analogues of 2'',3''-dideoxycytidine (ddeCyd) and 2'',3''-dideoxythymidine (ddeThd), 3''-azido-2'',3''-dideoxythymidine (AzddThd), 3''-fluoro-2'',3''-dideoxythymidine, 2'',3''-dideoxycytidine (ddCyd), and 2'',3''-dideoxyadenosine (ddAdo) emerged as the most potent inhibitors of HIV-induced cytopathogenicity in the human T lymphocyte cell lines ATH8 and MT4. In ATH8 cells ddCyd, ddeCyd, and ddAdo had the highest therapeutic index whereas in MT4 cells AzddThd, ddThd, ddCyd, and ddAdo were the most selective. Derivatives from ddThd in which the substituent group was linked to the 3''-carbon atom via a thio, sulfonyl, or oxygen bridge were far less inhibitory to HIV than was AzddThd.This publication has 17 references indexed in Scilit:
- INHIBITION OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE III IN VITRO BY PHOSPHONOFORMATEThe Lancet, 1985
- Inhibition of RNA-dependent DNA polymerases of AIDS and SAIDS retroviruses by HPA-23 (ammonium-21-tungsto-9-antimoniate)Annales de l'Institut Pasteur / Virologie, 1985
- Suramin Protection of T Cells in Vitro Against Infectivity and Cytopathic Effect of HTLV-IIIScience, 1984
- Synthesis and biological activity of various 3'-azido and 3'-amino analogs of 5-substituted pyrimidine deoxyribonucleosidesJournal of Medicinal Chemistry, 1983
- Isolation of Human T-Cell Leukemia Virus in Acquired Immune Deficiency Syndrome (AIDS)Science, 1983
- Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS)Science, 1983
- Species- or isozyme-specific enzyme inhibitors. 5. Differential effects of thymidine substituents on affinity for rat thymidine kinase isozymesJournal of Medicinal Chemistry, 1982
- Synthesis and antitumor activity of cytosine and adenine nucleosides of unsaturated 5-(aminoacyl)aminopentofuranosesCarbohydrate Research, 1980
- Design of species- or isozyme-specific enzyme inhibitors. I. Effect of thymidine substituents on affinity for the thymidine site of hamster cytoplasmic thymidine kinaseJournal of Medicinal Chemistry, 1979
- Nucleosidtransformationen, 2: Selektive Oxiranringöffnung von 9‐(2,3‐Anhydro‐β‐ D ‐ribofuranosyl)‐ und 9‐(2,3‐Anhydro‐β‐ D ‐lyxofuranosyl)adeninEuropean Journal of Inorganic Chemistry, 1976