Synthesis and biological evaluation of 2-oxonicotinonitriles and 2-oxonicotinonitrile based nucleoside analogues

Drug resistance and emergence of new pathogens highlight the need for developing new therapeutic agents. We focused on 2-oxonicotinonitrile (2-ONN) as derivative of the natural product 2-pyridinone.112-ONN: 2-oxonicotinonitrile. Herein, we describe the synthesis of 2-ONNs bearing two aryl groups, which we coupled with organohalides, including three glycosyl bromides, to prepare the nucleoside analogues. Coupling occurred mostly at the 2-ONN ring nitrogen to give the aimed targets, and in a few cases, it happened at the 2-oxo position giving O-alkylation products. Free 2-ONNs and their acetylated nucleosides were tested against a number of viruses. The nucleoside analogue 2aAc showed good anti SARS-CoV and anti influenza A (H5N1) activities. Additionally, 7b had good activity against Gram positive bacterium, Bacillis subtilis. [Display omitted] •2-Oxonicotinonitriles with two aryl groups were coupled with several organohalides.•The coupling occurred mostly at the ring nitrogen.•In a few cases, the coupling occurred at the 2-oxo position.•Antimicrobial and antiviral activities were tested for acetylated and free compounds.•One nucleoside analogue showed good anti SARS and anti influenza activity.