Synthesis and In Vitro Antiviral Evaluation of Novel 1-Arylpyrazoles and Their N- and S-Glycosides

A series of 1-arylpyrazole and their N- and S- glycosides has been synthesized. The key step is the synthesis of 3-(furan-2-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde 1 via Vilsmeier -Haack reaction on the hydrazone of 2-acetylfuran. Compound 1 was transformed to N, N-dialkyl acrylamide (and/or acetamide) derivatives 3a, 3b and 6 through reaction with malonic acid and application of Willgerodt-Kindler reaction followed by reaction with dialkylamine. Moreover, the aglycons 5-[3-(furan-2-yl)-1-phenyl-1H-pyrazol-4-yl]-1,3,4-oxadiazole-2(3H)-thione 10 and 6-(furan-2-yl)-4-[3-(furan-2-yl) -1-phenyl-1H-pyrazol-4-yl]-2-oxo -1,2-dihydro-pyridine-3-carbonitrile 14b were prepared and coupled with 2', 3', 4', 6'tetra- O-acetyl-alpha-D-gluco pyranosyl bromide under basic conditions to yield S-and N-glycoside derivatives 12 and 15, respectively. All the newly synthesized compounds were confirmed by IR, H-1 NMR, C-13 NMR and mass spectral studies. Antiviral activity was shown for most of the synthesized compounds. Compounds 4 and 14b exhibited a promising antiviral activity against vesicular stomatitis virus (VSV).