An approach to the identification of potent inhibitors of influenza virus fusion using parallel synthesis methodology (original) (raw)
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Salicylamide inhibitors of influenza virus fusion
Bioorganic & Medicinal Chemistry Letters, 2000
AbstractÐStructural variation of the quinolizidine heterocycle of the in¯uenza fusion inhibitor BMY-27709 was examined by several topological dissections in order to illuminate the critical features of the ring system. This exercise resulted in the identi®cation of a series of synthetically more accessible decahydroquinolines that retained the structural elements of BMY-27709 important for antiviral activity. The 2-methyl-cis-decahydroquinoline 6f was the most potent in¯uenza inhibitor identi®ed that demonstrated an EC 50 of 90 ng/mL in a plaque reduction assay. #
Novel quinolizidine salicylamide influenza fusion inhibitors
Bioorganic & Medicinal Chemistry Letters, 1999
A novel series of quinolizidine salicylamides was synthesized as specific inhibitors of the H1 subtype of influenza A viruses. These inhibitors inhibit the pH-induced fusion process, thereby blocking viral entry into host cells. Compound 16 was the most active inhibitor in this series with an ECs0 of 0.25 ~tg/mL in plaque reduction assay. The synthesis and the SAR of these compounds are discussed.
Archiv der Pharmazie, 2019
Hemagglutinin is the surface protein of the influenza virus that mediates both binding and penetration of the virus into host cells. We here report on the synthesis and structure-activity relationship of some novel N-(1-thia-4-azaspiro[4.5]decan-4-yl)carboxamide compounds carrying the 5-chloro-2-methoxybenzamide structure, designed as influenza virus fusion inhibitors. The carboxamides (1a-h, 2a-h) have a similar backbone structure as the fusion inhibitors that we reported on previously. Compounds 2b and 2d displayed inhibitory activity against influenza A/H3N2 virus replication (average antiviral EC 50 : 2.1 µM for 2b and 3.4 µM for 2d). Data obtained in the hemolysis inhibition assay supported that these compounds act as inhibitors of the influenza virus hemagglutinin-mediated fusion process.
Frontiers in cellular and infection microbiology, 2017
Influenza A virus is a negative RNA stranded virus of the family Orthomyxoviridae, and represents a major public health threat, compounding existing disease conditions. Influenza A virus replicates rapidly within its host and the segmented nature of its genome facilitates re-assortment, whereby whole genes are exchanged between influenza virus subtypes during replication. Antiviral medications are important pharmacological tools in influenza virus prophylaxis and therapy. However, the use of currently available antiviral is impeded by sometimes high levels of resistance in circulating virus strains. Here, we identified novel anti-influenza compounds through screening of chemical compounds synthesized de novo on human lung epithelial cells. Computational and experimental screening of extensive and water soluble compounds identified novel influenza virus inhibitors that can reduce influenza virus infection without detectable toxic effects on host cells. Interestingly, the indicated ac...