ArticleChemMedChem2025
Improved C5-Amide Bioisosteres for Human Neuraminidase 1 Inhibitors Based on 2-Deoxy-2,3-Didehydro-N-Acetyl Neuraminic Acid.
Article in ChemMedChem, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Neuraminidase enzymes (NEU) play a crucial role in many physiological and pathological conditions. Humans have four isoenzymes of NEU, and their specific roles continue to be investigated. Isoenzyme-selective inhibitors are needed as research tools and may lead to future therapeutics. A series of new candidate inhibitors are tested by replacing the C5-amide of 2-deoxy-2,3-dididehydro-N-acetyl neuraminic acid with amide bioisosteres. Design of candidate inhibitors is accomplished using substituents that are components of previously identified NEU inhibitors combined with alternative amide bioisosteres. Compounds are tested for inhibition of the four human NEU, and inhibitory activities are compared to reference amide compounds. 1,4-Disubstituted-1,2,3-triazole is the best bioisostere observed for inhibitors of NEU1. Inhibitor 542 shows high potency for NEU1 (K
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