Novel nucleosides as potent influenza viral inhibitors

Abstract

Influenza virus infection constitutes a significant health problem in need of more effective therapies. We have recently identified ((2 R,3 S,4 R,5 R)-3-acetoxy-5-(4-benzamido-2-oxopyrimidin-1(2 H)-yl)-4-fluoro-3,4-dimethyl-tetrahydrofuran-2-yl) methyl benzoate ( 18c) as a potent influenza virus inhibitor. We now here report the synthesis and evaluation of a series of C-3′ modified ribose nucleosides. These novel compounds were prepared, primarily by taking known ((2 R,3 R,4 R)-3-benzoyloxy-4-fluoro-4-methyl-5-oxo-tetrahydrofuran-2-yl)methyl benzoate ( 1) and converting it in to C-3 keto sugar ( 7), reacting C-3 keto group with methyl magnesium bromide, followed by coupling these sugars with purine and pyrimidine bases. Anti influenza viral activity was determined by screening against both A and B viral strains.