Synthesis of New Cyclic and Acyclic 5-Halouridine Derivatives as Potential Antiviral Agents

Abstract

The synthesis of new cyclic and acyclic nucleoside analogues was achieved by alkylation of 5-halogenated 6-(2,4-dichlorophenoxymethyl)pyrimidine-2,4-dione following the Vorbrüggen coupling procedure. Nucleoside analogues of the 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)-type were obtained as well as analogues of ganciclovir, acyclovir, and ribonucleosides. All compounds were tested against a variety of viruses. Three of the new compounds were potent and selective anti-HIV-1 inhibitors.

Key words

bioorganic chemistry - drugs - antiviral agents - nucleosides - glycosylation

References

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12

All new compounds were evaluated concerning their ability to inhibit the replication of HIV in T-lymphocytes cells. Briefly, a CEM cell suspension was infected with HIV-1 or HIV-2. The mutant thymidine kinase-deficient CEM cell cultures were only infected with HIV-2. Then, 100 µL of the infected cell suspensions was transferred into 96-well microtiter plate wells and mixed with 100 µL of the appropriate dilutions of the test compounds. After 4-5 days, giant cell formation was recorded microscopically in the HIV-infected cell cultures.