Design, synthesis, and biological evaluations of novel quinolones as HIV-1 non-nucleoside reverse transcriptase inhibitors

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 16; pp. 4246 - 4251
• Main Authors: Ellis, David, Kuhen, Kelli L., Anaclerio, Beth, Wu, Baogen, Wolff, Karen, Yin, Hong, Bursulaya, Badry, Caldwell, Jeremy, Karanewsky, Donald, He, Yun
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15-08-2006; Elsevier
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Binding Sites; Biological and medical sciences; Drug Resistance, Viral; HIV replication; HIV Reverse Transcriptase - antagonists & inhibitors; HIV-1 - metabolism; HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI); Medical sciences; Models, Chemical; Models, Molecular; Molecule modeling; Mutation; Pharmacology. Drug treatments; Quinolones; Quinolones - chemistry; Reverse Transcriptase Inhibitors - pharmacology; SAR; Structure-Activity Relationship; Virus Replication; HIV replication; Molecule modeling; HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI); SAR; Quinolones; RNA-directed DNA polymerase; HIV-1 virus; Non nucleoside compound; Modeling; Optimization; Structure activity relation; Reverse transcriptase inhibitor; Antiviral; Chemical synthesis; Quinolone derivatives; Enzyme; Transferases; Retroviridae; Enzyme inhibitor; Quinoline derivatives; Lentivirus; Virus; Nucleotidyltransferases; Replication; Human immunodeficiency virus
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2006.05.073

A novel series of quinolones was discovered as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) using a structure-based approach. The lead quinolones exhibited single digit nanomolar potency in the HIV-1 replication assays. The preliminary SAR of these quinolones was also established via systematic structural modifications. These novel and potent quinolones could serve as advanced leads for further optimization.