Document Report Card

ID: ALA1145959

Journal: J Med Chem

Title: Design and synthesis of 8-hydroxy-[1,6]naphthyridines as novel inhibitors of HIV-1 integrase in vitro and in infected cells.

Authors: Zhuang L, Wai JS, Embrey MW, Fisher TE, Egbertson MS, Payne LS, Guare JP, Vacca JP, Hazuda DJ, Felock PJ, Wolfe AL, Stillmock KA, Witmer MV, Moyer G, Schleif WA, Gabryelski LJ, Leonard YM, Lynch JJ, Michelson SR, Young SD.

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.

CiteXplore: 12570367

DOI: 10.1021/jm025553u