Linker-modified quinoline derivatives targeting HIV-1 integrase: synthesis and biological activity

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 10; pp. 2473 - 2476
• Main Authors: Bénard, Christophe, Zouhiri, Fatima, Normand-Bayle, Marie, Danet, Michèle, Desmaële, Didier, Leh, Hervé, Mouscadet, Jean-François, Mbemba, Gladys, Thomas, Claire-Marie, Bonnenfant, Sabine, Le Bret, Marc, d'Angelo, Jean
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 17.05.2004; Elsevier
• Subjects: Amides; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antivirals; Biochemistry, Molecular Biology; Biological and medical sciences; Cell Line; Cell Survival; Cell Survival - drug effects; Cross-Linking Reagents; Enzyme inhibitors; HIV Infections; HIV Infections - drug therapy; HIV Integrase; HIV Integrase - drug effects; HIV Integrase Inhibitors; HIV Integrase Inhibitors - chemical synthesis; HIV Integrase Inhibitors - pharmacology; Humans; Inhibitory Concentration 50; Life Sciences; Medical sciences; Molecular biology; Pharmacology. Drug treatments; Quinolines; Quinolines - chemical synthesis; Quinolines - pharmacology; Structure-Activity Relationship; Ureas; Virion; Virion - drug effects; Quinolines; Amides; Ureas; Enzyme inhibitors; Antivirals; Organic hydrazide; Nitro compound; Targeting; HIV-1 virus; Enzyme; Transferases; Retroviridae; Enzyme inhibitor; Quinoline derivatives; Subunit; Lentivirus; In vitro; Virus; Nucleotidyltransferases; Ex vivo; Functionalization; Structure activity relation; Carboxylic acid; Antiviral; Carboxamide; Aromatic compound; Human immunodeficiency virus; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.03.005

A series of quinoline derivatives linked to an aromatic ring by functionalized spacers was synthesized. The anti-HIV-1 integrase potency was evaluated in both in vitro and ex vivo assays. A novel series of HIV-1 integrase inhibitors was synthesized and tested in both in vitro and ex vivo assays. These inhibitors are featured by the presence of a quinoline subunit and an ancillary aromatic ring linked by functionalized spacers such as amide, hydrazide, urea and 1-hydroxyprop-1-en-3-one moiety. Amide derivatives are the most promising ones and could serve as leads for further developments.