Contemporary Medicinal Chemistry Strategies for the Discovery and Development of Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors
Zhao Wang, Srinivasulu Cherukupalli, Minghui Xie, Wenbo Wang, Xiangyi Jiang, Ruifang Jia, Christophe Pannecouque, Erik De Clercq, Dongwei Kang, Peng Zhan, Xinyong Liu
Abstract
Currently, HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) are a major component of the highly active anti-retroviral therapy (HAART) regimen. However, the occurrence of drug-resistant strains and adverse reactions after long-term usage have inevitably compromised the clinical application of NNRTIs. Therefore, the development of novel inhibitors with distinct anti-resistance profiles and better pharmacological properties is still an enormous challenge. Herein, we summarize state-of-the-art medicinal chemistry strategies for the discovery of potent NNRTIs, such as structure-based design strategies, contemporary computer-aided drug design, covalent-binding strategies, and the application of multi-target-directed ligands. The strategies described here will facilitate the identification of promising HIV-1 NNRTIs.