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

Eur J Med Chem. 2016 May 23:114:65-78. doi: 10.1016/j.ejmech.2016.02.051. Epub 2016 Feb 24.

Abstract

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.

Keywords: AIDS; CXCR4; Drug design; Entry inhibitors; HIV-1; Small molecular.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Drug Discovery*
  • HIV / drug effects*
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • CXCR4 protein, human
  • Receptors, CXCR4
  • Small Molecule Libraries