A new class of acyclic phosphonate nucleotide analogues: phosphonate isosteres of acyclovir and ganciclovir monophosphates as antiviral agents
| Autor: | Michael J. M. Hitchcock, Choung U. Kim, Ismail Ghazzouli, Peter F. Misco, Bing Yu Luh, John C. Martin |
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| Rok vydání: | 1991 |
| Předmět: |
Ganciclovir
Herpesvirus 3 Human Chemical Phenomena Isostere Stereochemistry Guanine viruses Acyclovir Cytomegalovirus Antiviral Agents chemistry.chemical_compound Mice Structure-Activity Relationship Culture Techniques Drug Discovery medicine Animals Simplexvirus Nucleotide skin and connective tissue diseases Purine metabolism chemistry.chemical_classification Nucleotides virus diseases Biological activity Phosphonate Chemistry chemistry Molecular Medicine Cytosine medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 34(7) |
| ISSN: | 0022-2623 |
| Popis: | Novel phosphonate isosteres of acyclovir (ACV) and ganciclovir (DHPG) monophosphates were found to be potent and selective antiherpesvirus agents. In the series of phosphonate analogues of ACV monophosphate, only the guanine analogue 20 exhibited activity against herpesviruses, similar to the structure-activity relationship observed for base modification of ACV analogues. The phosphonate isostere of ACV monophosphate (20) was more effective than ACV in the HSV-1 infected mouse model. The 3'-carba analogues of 9-[3-hydroxy-2-(phosphonomethoxy)propyl]purines/pyrimidines (adenine, HPMPA; guanine, HPMPG; cytosine, HPMPC) are devoid of antiherpesvirus activity. This result confirms that the beta-oxygen atom of the phosphonomethyl ether functionality in HPMP-purines/pyrimidines plays a critical role for activity against herpesviruses. |
| Databáze: | OpenAIRE |
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