Synthesis and Antiviral Activity of the Carbocyclic Analogue of the Highly Potent and Selective Anti-VZV Bicyclo Furano Pyrimidines
Citations Over Time
Abstract
Carbocyclic nucleoside analogues are catabolically stable since they are resistant to phosphorolytic cleavage by pyrimidine nucleoside phosphorylase enzymes. The carbocyclic analogue (C-BCNA) of the highly potent and selective anti-VZV bicyclic nucleoside analogue (BCNA) 6-pentylphenylfuro[2,3-d]pyrimidine-2'-deoxyribose was synthesized using carbocyclic 2'-deoxyuridine as starting material. C-BCNA was found to be chemically more stable than the furano lead, but it was shown to be significantly less antivirally active than its parent nucleoside analogue. It was noted to have a 10-fold lower inhibitory activity against the VZV-encoded thymidine kinase. This reduction of activity may be attributed to the different conformation of the sugar and base, as predicted by computational studies and supported by NMR studies. However, other factors besides affinity for VZV-TK must account for the greatly reduced antiviral potency.
Related Papers
- → Role of Platelet Derived Endothelial Cell Growth Factor/Thymidine Phosphorylase in Fluoropyrimidine Sensitivity and Potential Role of Deoxyribose‐1‐Phosphate(2004)14 cited
- → Role of Platelet Derived Endothelial Cell Growth Factor/Thymidine Phosphorylase in Fluoropyrimidine Sensitivity and Potential Role of Deoxyribose‐1‐phosphate(2005)2 cited
- → Enzymes of Purine Interconversions in Subfractions of Lymphocytes(1980)6 cited
- → Enzymatic Synthesis of 2′,5′-Dideoxv Purine Nucleosides and Related Compounds(1997)4 cited
- [Prediction of prognosis of patients with gastrointestinal cancer based on thymidine uptake].(1994)