Design of Non-nucleoside Inhibitors of HIV-1 Reverse Transcriptase with Improved Drug Resistance Properties. 2

• Published in: Journal of medicinal chemistry Vol. 47; no. 24; pp. 5923 - 5936
• Main Authors: Freeman, George A, Andrews, C. Webster, Hopkins, Andrew L, Lowell, Gina S, Schaller, Lee T, Cowan, Jill R, Gonzales, Stephen S, Koszalka, George W, Hazen, Richard J, Boone, Lawrence R, Ferris, Rob G, Creech, Katrina L, Roberts, Grace B, Short, Steven A, Weaver, Kurt, Reynolds, David J, Milton, John, Ren, Jingshan, Stuart, David I, Stammers, David K, Chan, Joseph H
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 18.11.2004; Amer Chemical Soc
• Subjects: Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Benzoxazines; Binding Sites; Biological and medical sciences; Cell Line; Chemistry, Medicinal; Crystallography, X-Ray; Drug Design; Drug Resistance, Viral; HIV Reverse Transcriptase - chemistry; HIV Reverse Transcriptase - genetics; HIV Reverse Transcriptase - metabolism; HIV-1 - drug effects; HIV-1 - enzymology; Human immunodeficiency virus 1; Humans; Life Sciences & Biomedicine; Medical sciences; Models, Molecular; Molecular Structure; Mutation; Oxazines - chemistry; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Quinolones - chemical synthesis; Quinolones - chemistry; Quinolones - pharmacology; Reverse Transcriptase Inhibitors - chemical synthesis; Reverse Transcriptase Inhibitors - chemistry; Reverse Transcriptase Inhibitors - pharmacology; Science & Technology; Structure-Activity Relationship; SYSTEM; COMPLEX; REPLICATION; ACID; DMP-266; EFAVIRENZ; CRYSTALLOGRAPHY; MUTATIONS; DERIVATIVES; Cyclopropane derivatives; RNA-directed DNA polymerase; Acetylenic compound; HIV-1 virus; Nitrogen heterocycle; Non nucleoside compound; Lactam; Binding site; Modeling; Structure activity relation; Molecular model; Bicyclic compound; Antiviral; Aromatic compound; Chemical synthesis; Treatment resistance; Enzyme; Transferases; Retroviridae; Enzyme inhibitor; Inhibitor enzyme complex; Lentivirus; X ray diffraction; In vitro; Virus; Nucleotidyltransferases; Fluorine Organic compounds; Human immunodeficiency virus; Crystalline structure
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm040072r

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.