Synthesis and antiviral activity of certain guanosine analogs in the thiazolo[4,5-d]pyrimidine ring system
| Autor: | Jack D. Anderson, Arthur F. Lewis, Yogesh S. Sanghvi, Howard B. Cottam, Ganesh D. Kini, Roland K. Robins, Ganapathi R. Revankar, Donald F. Smee |
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| Rok vydání: | 1991 |
| Předmět: |
Glycosylation
Guanosine Pyrimidine Chemistry Stereochemistry Purine analogue Biological activity Purine Nucleosides Antiviral Agents Semliki forest virus Chemical synthesis Mice chemistry.chemical_compound Sodium borohydride Togaviridae Infections Drug Discovery Animals Molecular Medicine Female Prodrugs Nucleoside |
| Zdroj: | Journal of Medicinal Chemistry. 34:3006-3010 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | Several sugar-modified nucleoside derivatives of the purine analogue 5-amino-3-beta-D-ribofuranosylthiazolo[4,5-d]pyrimidine-2,7-dione (1) were synthesized. Phosphorylation of 1 using POCl3 resulted in 5'-monophosphate 2, which was subsequently converted to 3',5'-cyclic phosphate 3, by reported methods. 5'-Sulfamoyl derivative 4 was synthesized by treatment of the 2,3-O-isopropylidene derivative of 1 with chlorosulfonamide followed by acid deprotection. Compounds 5-7, the 5'-deoxy, the tri-O-acetyl, and the 2'-deoxy derivatives of 1, respectively, were synthesized by glycosylation of 5-aminothiazolo[4,5-d]pyrimidine-2,7-dione, the aglycon of 1, with the appropriate sugar moieties, utilizing the Vorbruggen procedure. Oxidative cleavage of the C2'-C3' bond in 1 followed by reduction with sodium borohydride led to "seco" analogue 8. Nucleosides 2-8 were evaluated for antiviral activity in vivo against the Semliki Forest virus. The activity of compounds 2, 5, and 7 were similar to that of 1. Cyclic phosphate 3 was toxic at the high dose and weakly active at the lower dose. Compounds 4, 6, and 8 were inactive in this system. |
| Databáze: | OpenAIRE |
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