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Discovery and Development of Zidovudine as the Cornerstone of Therapy to Control Human Immunodeficiency Virus Infection

  • Kathryn H. Pattishall

Abstract

From the time Dr. George Hitchings began the research program at Wellcome Research Laboratories in 1942 to search for antagonists of nucleic acid bases, viruses were among the potential chemotherapeutic targets. A number of 5-substituted uracil derivatives and 2,6-diaminopurine, which had been identified as inhibitors of bacterial nucleic acid synthesis in Lactobacillus casei, were found to also interfere in tissue culture with the multiplication of vaccinia virus, a DNA virus. Simultaneously, the laboratory had discovered a new antiparasitic drug, pyrimethamine, a pyrimidine, to treat malaria and toxoplasmosis, and a new antileukemic drug, 6-mercaptopurine, in the purine series. As a result, extensive efforts were devoted to bringing these to clinical use. Unfortunately, the antiviral agents had to take a back seat, particularly because the toxicity of 2,6-diaminopurine to bone marrow discouraged further pursuit of this lead at levels required for antiviral activity. It was over ten years later that the deoxyribosides of 5-iodouracil, 5-chlorouracil, and 5-trifluoromethyluracil were synthesized by others and found to have activity against the herpes viruses. While two of these deoxynucleosides (5-iodo- and 5-trifluoromethyluracil) were clinically useful topically for herpes keratitis, they were too toxic to be employed systemically.

Keywords

Thymidine Kinase Antimicrob Agent Yellow Fever Virus Intravenous Drug Abuser Plaque Reduction Assay 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Kathryn H. Pattishall

There are no affiliations available

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