An investigation of phenylthiazole antiflaviviral agents.

Mayhoub AS, Khaliq M, Botting C, Li Z, Kuhn RJ, Cushman M.

Citation

Mayhoub AS, Khaliq M, Botting C, Li Z, Kuhn RJ, Cushman M. (2011) An investigation of phenylthiazole antiflaviviral agents. Bioorganic and Medicinal Chemistry 19(12):3845-3854.

Abstract

Flaviviruses are one of the most clinically important pathogens and their infection rates are increasing steadily. The phenylthiazole ring system has provided a template for the design and synthesis of antiviral agents that inhibit the flaviviruses by targeting their E-protein. Unfortunately, there is a correlation between phenylthiazole antiflaviviral activity and the presence of the reactive and therefore potentially toxic mono- or dibromomethyl moieties at thiazole-C4. Adding a linear hydrophobic tail para to the phenyl ring led to a new class of phenylthiazole antiflaviviral compounds that lack the toxic dibromomethyl moiety. This led to development of a drug-like phenylthiazole 12 that had high antiflaviviral selectivity (TI=147).