Discovery of non-peptide small molecular CXCR4 antagonists as anti-HIV agents: Recent advances and future opportunities

•We reviewed recent advances on small molecular CXCR4 antagonists.•We focused on the evolution of CXCR4 and structure-activity relationships of representative CXCR4 antagonists.•We introduced the medicinal chemistry strategies and novel methodologies.

CXCR4 plays vital roles in HIV-1 life cycle for it's essential in mediating the interaction of host and virus and completing the entry process in the lifecycle of HIV-1 infection. Compared with some traditional targets, CXCR4 provides a novel and less mutated drug target in the battle against AIDS. Its antagonists have no cross resistance with other antagonists. Great achievements have been made recent years and a number of small molecular CXCR4 antagonists with diversity scaffolds have been discovered. In this review, recent advances in the discovery of CXCR4 antagonists with special attentions on their evolution and structure-activity relationships of representative CXCR4 antagonists are described. Moreover, some classical medicinal chemistry strategies and novel methodologies are also introduced.

Graphical abstractRecent advances in the discovery of CXCR4 antagonists with special attentions on their evolution and structure-activity relationships of representative CXCR4 antagonists.Figure optionsDownload full-size imageDownload as PowerPoint slide