Pridine Oxide Derivatives: Structure-Activity Relationship for Inhibition of Human Immunodeficiency Virus and Cytomegalovirus Replication in Cell Culture

• Published in: Helvetica chimica acta 2002-09, Vol.85 (9), p.2961-2974
• Main Authors: Balzarini, Jan, Stevens, Miguel, Andrei, Graciela, Snoeck, Robert, Strunk, Richard, Pierce, James B., Lacadie, John A., De Clercq, Erik, Pannecouque, Christophe
• Format: Article
• Language: English
• Subjects: Cytomegalovirus; Human cytomegalovirus; Human immunodeficiency virus 1; Human immunodeficiency virus 2
• ISSN: 0018-019X; 1522-2675
• DOI: 10.1002/1522-2675(200209)85:9<2961::AID-HLCA2961>3.0.CO;2-R

Novel pyridine oxide derivatives have been discovered that are endowed with inhibitory potential against human immunodeficiency virus (HIV) and cytomegalovirus (CMV) in cell culture. The compounds show different antiviral specificities (solely active or concomitantly active against HIV‐1 and/or HIV‐2 and/or CMV) depending on the nature and the specific location of the substituents on the different parts of the molecule. The HIV‐1‐specific pyridine oxide derivatives have the highest selectivity index, and act as specific HIV‐1 non‐nucleoside reverse transcriptase inhibitors (NNRTIs). For other pyridine oxide derivatives, it cannot be excluded that a cellular target may be involved to explain the concomitant activity against HIV‐1, HIV‐2, and CMV. The latter compounds showed a relatively low selectivity index and were, in general, more cytostatic than the HIV‐1‐specific inhibitors.