Design and Synthesis of 8-Hydroxy-[1,6]Naphthyridines as Novel Inhibitors of HIV-1 Integrase in Vitro and in Infected Cells
- 9 January 2003
- journal article
- letter
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 46 (4) , 453-456
- https://doi.org/10.1021/jm025553u
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 μM. It does not exhibit cytotoxicity in cell culture at ≤12.5 μM 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.Keywords
This publication has 7 references indexed in Scilit:
- Diketo acid inhibitor mechanism and HIV-1 integrase: Implications for metal binding in the active site of phosphotransferase enzymesProceedings of the National Academy of Sciences, 2002
- Inhibitors of Strand Transfer That Prevent Integration and Inhibit HIV-1 Replication in CellsScience, 2000
- Cell protein cross-linking by erbstatin and related compoundsBiochemical Pharmacology, 1996
- One Step Reduction of Diaryl Ketones to Hydrocarbons by Etherated Boron Trifluoride-Triethylsilane SystemSynthetic Communications, 1994
- L-735,524: an orally bioavailable human immunodeficiency virus type 1 protease inhibitor.Proceedings of the National Academy of Sciences, 1994
- Palladium-catalyzed α-arylation of vinyl butyl ether with aryl halidesTetrahedron Letters, 1991
- Synthesis and Polymerization of PropanesultamThe Journal of Organic Chemistry, 1963