Authentic HIV-1 integrase inhibitors. (July 2010)

• Record Type: Journal Article
• Authors: Liao, Chenzhong; Marchand, Christophe; Burke Jr, Terrence R; Pommier, Yves; Nicklaus, Marc C
• Is Part Of: Future medicinal chemistry. Volume 2:Number 7(2010)
• Page Start: 1107
• Page End: 1122
• Publication Date: 2010-07
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.4155/fmc.10.199
• Languages: English
• ISSNs: 1756-8919

Abstract

HIV-1 integrase (IN) is indispensable for HIV-1 replication and has become a validated target for developing anti-AIDS agents. In two decades of development of IN inhibition-based anti-HIV therapeutics, a significant number of compounds were identified as IN inhibitors, but only some of them showed antiviral activity. This article reviews a number of patented HIV-1 IN inhibitors, especially those that possess high selectivity for the strand transfer reaction. These compounds generally have a polar coplanar moiety, which is assumed to chelate two magnesium ions in the binding site. Resistance to those compounds, when given to patients, can develop as a result of IN mutations. We refer to those compounds as authentic IN inhibitors. Continued drug development has so far delivered one authentic IN inhibitor to the market (raltegravir in 2007). Current and future attention will be focused on the development of novel authentic IN inhibitors with the goal of overcoming viral resistance.