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

Abstract

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-α-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, 1H NMR, 13C 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). Keywords: Antiviral Activity, Cytotoxicity, N-Nucleosides, Oxadiazoles, Pyrazoles, Thioglycosides, anticoagulant activity, S- Glycosides, 1H NMR, N- Glycosides, t vesicular stomatitis virus (VSV)., β-substituted acrylic acid, N, N- dimethylacetamide derivative, Acetamide, Esterification, hydrazinolysis