Studies of Anti-HIV Transcription Inhibitor Quinolones: Identification of Potent N1-Vinyl Derivatives

✍ Scribed by Prof. Oriana Tabarrini; Dr. Serena Massari; Dr. Dirk Daelemans; Dr. Francesco Meschini; Dr. Giuseppe Manfroni; Dr. Laura Bottega; Prof. Barbara Gatto; Prof. Manlio Palumbo; Prof. Christophe Pannecouque; Prof. Violetta Cecchetti

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 416 KB
• Volume: 5
• Category: Article
• ISSN: 1860-7179
• DOI: 10.1002/cmdc.201000267

✦ Synopsis

Abstract

The 6‐desfluoroquinolones (6‐DFQs) are anti‐HIV agents that target Tat‐mediated transcription. This particular mechanism of action makes this class of compounds very attractive for further structural investigations. Identification of the pharmacophore required for inhibition will ultimately result in the design of more selective analogues for use in combination therapy for the treatment of HIV infections. We have focused on the pyridone ring of the quinolone nucleus present in these compounds, designing new modifications to broaden the structure–activity relationship knowledge base. Herein, we present novel and very potent anti‐HIV quinolones, most notably those bearing an amino or vinyl group at the N1 position. Attempts were made to determine the structural parameters necessary to impart potent anti‐HIV activity to the vinyl derivatives.