6th International AIDS Conference


San Francisco, California, USA — June 20-23, 1990

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Novel phosphate pro-drugs of AZT.

Int Conf AIDS 1990 Jun 20-23; 6:329 (abstract no. 1062)
McGuigan C, Devine KG, O'Connor TJ, Kinchington D; Dept. Chemistry, University College London, London, UK

OBJECTIVE: Phosphate triester derivatives of 3'-Azido-3'-deoxythymidine (AZT) have been investigated as anti-HIV agents.

METHODS: Phosphate triesters have been synthesised by phosphoramidate methodologies, have been fully characterised, and have been tested against HIV-1 in a lymphoblastoid cell line.

RESULTS: Over 50 novel derivatives have been prepared. The compounds show potent inhibition of viral proliferation, with ED50 values below 1 muM. The precise activity is very dependent on the exact phosphate structure, and a number of Structure-Activity relationships have emerged. In particular, phosphoramidates are especially active, with minor structural changes in the amino region leading to significant changes in activity. All of the compounds in the series are non-toxic to un-infected cells at 100 muM. Data indicate that the compounds may act as intracellular sources of the bio-active nucleotides.

CONCLUSION: Structures of this type may be useful as pro-drugs in HIV chemotherapy.

Keywords: AEGIS, Zidovudine, Prodrugs, HIV-1, Phosphates, Antiviral Agents, Anti-HIV Agents, HIV, Phosphoric Acids, HIV Infections, Nucleotides, Amides, Structure-Activity Relationship, phosphoramidic acid, ICA6KWDaegis,zidovudine,prodrugs,hiv-1,phosphates,antiviralagents,anti-hivagents,hiv,phosphoricacids,hivinfections,nucleotides,amides,structure-activityrelationship,phosphoramidicacid,ica6

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