Antiherpes activity of (E)-5-(2-bromovinyl)- and 5-vinyl-1-β-D-arabinofuranosyluracil and some other 5-substituted uracil arabinosyl nucleosides in two different cell lines

Synthesis and Evaluation of Some Uracil Nucleosides as Promising Anti-Herpes Simplex Virus 1 Agents

“…The 1 H-NMR showed the appearance of the free OH protons in the range δ ≈ 4.5-4.9 ppm. Cyclic nucleosides (9-11) were prepared via the reaction of silyated pyrimidine 2 with various activated cyclic sugars, namely, 1-acetate-2,3,5-tri-0-benzoate-ß-D-ribofuranose iv, 2-deoxy-3,5-di-0-p-chlorobenzoyl-D-ribofuranosyl chloride v and 1-bromo-2,3,4-tetra-0-acetyl-ß-D-glucopyranose vi as reported in [9,50,51], giving the protected nucleosides 9, 10 and 11 as a ß-anomers. 1 H-NMR showed a doublet signal in the range δ≈ 6.20-6.48 ppm, corresponding to the anomeric proton of a sugar moiety with a coupling constant (J1,2 = 9.10-9.50 Hz) that was attributed to the diaxial orientation of H-1 and H-2 protons, indicating the presence of a ß-configuration.…”

Small Molecule Drugs Targeting Viral Polymerases

“…Conversely, the 5-(2-bromovinyl) nucleoside analogue BVDU displays selective activation solely within cells infected by VZV and HSV-1, possessing a stronger affinity for the viral polymerases [57][58][59]. This heightened selectivity and activity profile stem from specific phosphorylation by the virus-encoded thymidine kinase of the E isomer of BVDU, [56,60], which is approximately one hundred-fold more active than the Z form [61,62]. It is worth noting that this NI was approved for use outside United States (U.S.), specifically in a number of European countries including Austria, Belgium, Germany, Greece, Italy, Portugal, Spain, and Switzerland.…”

Synthesis and biological activities of 4-O-(difluoromethyl)-5-substituted-uracil nucleoside analogs

“…(E,)-l-d-D-Arabinofuranosyl-4-0-(difluoromethyl)-5-(2bromoviny 1)uracil (5g). Compound 2g (3 mmol, 1.04 g) yielded 0.55 g (1.4 mmol, 46.2%) of 5g following the above-mentioned procedure: mp 199-203 °C dec; MS, m/e 396/398 (M+); XH NMR (Me2SO-d6) 8.25 (s, 1, H-6), 7.70 (t, 1, 2Jh,f = 57 Hz, OCF2H), 7.42 (d, 1,3=7cH,CHBr = 14 Hz, CH bromovinyl group), 7.05 (d, 1, sdcHBr,CH = 14 Hz, CHBr), 6.43 (d, 1, 3=/h.Fih-2 = 4.5 Hz, H-l'), 4.01-3.7 (m, 3, H-2', H-3', H-4'), 3.54 (m, 2, CH2C-5'); UV Xmax (H20) 305 nm (e 5360). Anal.…”

“…Their inhibition data obtained in present investigations correspond to previously reported values. 14 ACV and araT exhibited a 50% inhibition of HSV-1 plaque formation (ID60) at concentrations of 0.48 and 0.64 µ , respectively, whereas BrV-araU and BrV-dUrd were nearly 5-10 times more effective (Table I). In contrast to BrV-araU and BrV-dUrd, which displayed a nearly 500-fold lower inhibitory effect against HSV-2 compared with HSV-1, ACV and araT were only 2-3-fold less active against HSV-2.…”