Design and Synthesis of 8-Hydroxy-[1,6]Naphthyridines as Novel Inhibitors of HIV-1 Integrase in Vitro and in Infected Cells
Journal of Medicinal Chemistry2003Vol. 46(4), pp. 453–456
Citations Over TimeTop 10% of 2003 papers
Linghang Zhuang, John Wai, Mark W. Embrey, Thorsten E. Fisher, Melissa S. Egbertson, Linda S. Payne, James P. Guare, Joseph P. Vacca, Daria J. Hazuda, Peter J. Felock, Abigail Wolfe, Kara A. Stillmock, Marc Witmer, Gregory Moyer, William A. Schleif, Lori J. Gabryelski, Yvonne Leonard, Joseph J. Lynch, Stuart R. Michelson, Steven D. Young
Abstract
Naphthyridine 7 inhibits the strand transfer of the integration process catalyzed by integrase with an IC50 of 10 nM and inhibits 95% of the spread of HIV-1 infection in cell culture at 0.39 microM. It does not exhibit cytotoxicity in cell culture at < or =12.5 microM and shows a good pharmacokinetic profile when dosed orally to rats. The antiviral activity of 7 and its effect on integration were confirmed using viruses with specific integrase mutations.
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