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Thiazolides as novel antiviral agents. 1. Inhibition of hepatitis B virus replication

Stachulski, A.V., Pidathala, C., Row, E.C., Sharma, R., Berry, N.G., Iqbal, M., Bentley, J., Allman, S.A., Edwards, G., Helm, A., Hellier, J., Korba, B.E., Semple, J.E. and Rossignol, J.-F. (2011) Thiazolides as novel antiviral agents. 1. Inhibition of hepatitis B virus replication. Journal of Medicinal Chemistry, 54 (12). pp. 4119-4132. ISSN 0022-2623

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To link to this item DOI: 10.1021/jm200153p


We report the syntheses and activities of a wide range of thiazolides [viz., 2-hydroxyaroyl-N-(thiazol-2-yl)amides] against hepatitis B virus replication, with QSAR analysis of our results. The prototypical thiazolide, nitazoxanide [2-hydroxybenzoyl-N-(5-nitrothiazol-2-yl)amide, NTZ] 1 is a broad spectrum antiinfective agent effective against anaerobic bacteria, viruses, and parasites. By contrast, 2-hydroxybenzoyl-N-(5-chlorothiazol-2-yl)amide 3 is a novel, potent, and selective inhibitor of hepatitis B replication (EC50 = 0.33 μm) but is inactive against anaerobes. Several 4′- and 5′-substituted thiazolides show good activity against HBV; by contrast, some related salicyloylanilides show a narrower spectrum of activity. The ADME properties of 3 are similar to 1; viz., the O-acetate is an effective prodrug, and the O-aryl glucuronide is a major metabolite. The QSAR study shows a good correlation of observed EC90 for intracellular virions with thiazolide structural parameters. Finally we discuss the mechanism of action of thiazolides in relation to the present results.

Item Type:Article
Divisions:No Reading authors. Back catalogue items
Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Medicinal Chemistry Research Group
ID Code:89156
Publisher:American Chemical Society

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