Pyrimidine Thioethers: A Novel Class of HIV-1 Reverse Transcriptase Inhibitors with Activity Against BHAP-Resistant HIV
| Autor: | Stephen T. Schlachter, Richard C. Thomas, T. J. Poel, David R. Graber, Robert A. Olmsted, Laurice A. Kopta, Megan Murphy, Richard A. Nugent, S M Swaney, Keiser Bj, Joel Morris, Y. Yagi, Cleek Gary J, W G Tarpley, S M Poppe, Donn G. Wishka |
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| Rok vydání: | 1998 |
| Předmět: |
Proline
Pyrimidine Anti-HIV Agents Sulfides Cell Line Mice Structure-Activity Relationship chemistry.chemical_compound Thioether Leucine Drug Discovery medicine Animals Structure–activity relationship Delavirdine chemistry.chemical_classification biology Drug Resistance Microbial Nucleotidyltransferase HIV Reverse Transcriptase Reverse transcriptase Pyrimidines Enzyme Amino Acid Substitution chemistry Biochemistry Enzyme inhibitor HIV-1 biology.protein Reverse Transcriptase Inhibitors Molecular Medicine medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 41:3793-3803 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm9800806 |
| Popis: | A series of pyrimidine thioethers was synthesized and evaluated for inhibitory properties against wild-type HIV-1 reverse transcriptase (RT) and an RT carrying the resistance-conferring mutation P236L. Modifications of both the pyrimidine and the functionality attached through the thioether yielded several analogues, which demonstrated activity against both enzyme types, with IC50 values as low as 190 nM against wild-type and 66 nM against P236L RT. Evaluation of a select number of pyrimidine thioethers in cell culture showed that these compounds have excellent activity against HIV-1IIIB-WT and retain good activity against a laboratory-derived HIV-1MF delavirdine-resistant variant. |
| Databáze: | OpenAIRE |
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