Synthesis and Evaluation of a Series of 2′-Deoxy Analogues of The Antiviral Agent 5,6-Dichloro-2-Isopropylamino-1-(β-L-Ribofuranosyl)-1H-Benzimidazole (1263W94)
| Autor: | Lloyd Frick, John C. Drach, Joseph H. Chan, Dean W. Selleseth, Stanley D. Chamberlain, George W. Koszalka, Ernest H. Dark, Robert J. Harvey, Karen K. Biron, Leroy B. Townsend, R E Dornsife, Michelle G. Davis |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Benzimidazole Magnetic Resonance Spectroscopy Stereochemistry Biological Availability Cytomegalovirus Mice Inbred Strains Plasma protein binding Antiviral Agents Biochemistry Mice chemistry.chemical_compound Pharmacokinetics Genetics medicine Animals Humans Moiety Cytotoxicity Cells Cultured General Medicine Nuclear magnetic resonance spectroscopy Bioavailability chemistry Mechanism of action Molecular Medicine Benzimidazoles Ribonucleosides medicine.symptom |
| Zdroj: | Nucleosides, Nucleotides and Nucleic Acids. 19:101-123 |
| ISSN: | 1532-2335 1525-7770 |
| Popis: | A series of 2'-deoxy analogues of the antiviral agent 5,6-dichloro-2-isopropylamino-1-(beta-L-ribofuranosyl)-1H-benzimidazole (1263W94) were synthesized and evaluated for activity against human cytomegalovirus (HCMV) and for cytotoxicity. The 2-substituents in the benzimidazole moiety correspond to those that were used in the 1263W94 series. In general, as was found in the 1263W94 series, cyclic and branched alkylamino groups were needed for potent activity against HCMV. Three analogues 3a, 3b and 3d were as potent as 1263W94. Further evaluation of two analogues, 3a and 3b, suggested that these 2'-deoxy analogues may act via a novel mechanism of action similar to that of 1263W94. These 2'-deoxy analogues generally lacked cytotoxicity in vitro. Pharmacokinetic parameters in mice and protein binding properties of 3a were quite similar to 1263W94. However, the oral bioavailability of 3a was only half of that observed for 1263W94. |
| Databáze: | OpenAIRE |
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