Synthesis and antiviral activity of some 3'-C-difluoromethyl and 3'-deoxy-3'-C-fluoromethyl nucleosides
| Autor: | M. J. Bamford, Richard T. Walker, Paul L. Coe |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Herpesvirus 3
Human Chemical Phenomena Hydrocarbons Fluorinated Stereochemistry Varicella zoster virus Human immunodeficiency virus (HIV) Uracil Biological activity Nucleosides medicine.disease_cause Sulfur trifluoride Antiviral Agents Trifluridine chemistry.chemical_compound Chemistry Structure-Activity Relationship chemistry Drug Discovery medicine HIV-1 Molecular Medicine Cytotoxicity Nucleoside |
| Zdroj: | Journal of medicinal chemistry. 33(9) |
| ISSN: | 0022-2623 |
| Popis: | The synthesis and antiviral activity of a number of 3'-C-difluoromethyl and 3'-deoxy-3'-C-fluoromethyl nucleosides are reported. The 3'-C-difluoromethyl nucleosides 26a and 26b were obtained by treatment of the corresponding 2',5'-di-O-protected-3'-C-formyl nucleosides 25a and 25b with (diethylamino)sulfur trifluoride (DAST). Removal of the 2'-O-protecting group from 26a and subsequent reaction with DAST furnished the 2'-deoxy-2'-fluoro-beta-D-ribo-pentofuranosyl nucleoside 29. Selective fluorination with DAST of the 5'-O-protected analogues 3'-deoxy-3'-C-hydroxymethyl derivatives 13a and 13b gave the 3'-deoxy-3'-C-fluoromethyl derivatives 30a and 30b, while nonselective fluorination afforded the 2',3'-dideoxy-2'-fluoro-3'-C-fluoromethyl analogues 31a and 31b. The deprotected uracil analogue 17a was iodinated to the 5-iodouracil derivative 18. The fully deprotected fluorinated 3'-C-branched nucleosides 14-18 and 32 were evaluated for their antiviral activity. None were active against human immunodeficiency virus type-1 (HIV-1) at concentrations up to 100 microM. However, 5-iodouracil analogue 18 showed activity, comparable to that of acyclovir, against varicella zoster virus without observed cytotoxicity. |
| Databáze: | OpenAIRE |
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