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

ABSTRACT: 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.(1) 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 2a(Ac) showed good anti SARS-CoV and anti influenza A (H?N?) activities. Additionally, 7b had good activity against Gram positive bacterium, Bacillis subtilis.

SUBMITTER: Abou-Elkhair RA

PROVIDER: S-EPMC7115408 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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

Abou-Elkhair Reham A I RA Moustafa Ahmed H AH Haikal Abdelfattah Z AZ Ibraheem Ahmed M AM

European journal of medicinal chemistry 20140108

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.(1) 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- ...[more]

PMID: 24486419

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