Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved drug resistance properties. 2.

Journal article

HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs) are part of the combination therapy currently used to treat HIV infection. The features of a new NNRTI drug for HIV treatment must include selective potent activity against both wild-type virus as well as against mutant virus that have been selected by use of current antiretroviral treatment regimens. Based on analogy with known HIV-1 NNRTI inhibitors and modeling studies utilizing the X-ray crystal structure of inhibitors bound in the HIV-1 RT, a series of substituted 2-quinolones was synthesized and evaluated as HIV-1 inhibitors.

Authors: Freeman, G; Andrews, C; Hopkins, A; Lowell, G; Schaller, LT

• Publication status: Published
• Journal: Journal of medicinal chemistry
• Volume: 47
• Issue: 24
• Pages: 5923-5936
• Publication date: 2004-11-01
• DOI: 10.1021/jm040072r
• EISSN: 1520-4804
• ISSN: 0022-2623
• Language: English
• Keywords: Drug Design; Drug Resistance, Viral; Anti-HIV Agents; Molecular Structure; Structure-Activity Relationship; HIV Reverse Transcriptase; Quinolones; Oxazines; Cell Line; Models, Molecular; HIV-1; Reverse Transcriptase Inhibitors; Binding Sites; Mutation; Humans; Benzoxazines; Crystallography, X-Ray