Synthesis and SAR of novel isoquinoline CXCR4 antagonists with potent anti-HIV activity

Bioorg Med Chem Lett. 2010 May 15;20(10):3026-30. doi: 10.1016/j.bmcl.2010.03.118.


Using AMD070 as a starting point for structural modification, a novel series of isoquinoline CXCR4 antagonists was developed. A structure-activity scan of alternate lower heterocycles led to the 3-isoquinolinyl moiety as an attractive replacement for benzimidazole. Side chain optimization in the isoquinoline series led to a number of compounds with low nanomolar anti-HIV activities and promising rat PK properties.

MeSH terms

  • Animals
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacokinetics
  • Benzimidazoles / chemistry
  • Isoquinolines / chemical synthesis
  • Isoquinolines / chemistry*
  • Isoquinolines / pharmacokinetics
  • Rats
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Receptors, CXCR4 / metabolism
  • Structure-Activity Relationship


  • Anti-HIV Agents
  • Benzimidazoles
  • Isoquinolines
  • Receptors, CXCR4
  • benzimidazole