Synthesis and SAR of novel CXCR4 antagonists that are potent inhibitors of T tropic (X4) HIV-1 replication

Bioorg Med Chem Lett. 2011 Jan 1;21(1):262-6. doi: 10.1016/j.bmcl.2010.11.023. Epub 2010 Nov 6.

Abstract

An early lead from the AMD070 program was optimized and a structure-activity relationship was developed for a novel series of heterocyclic containing compounds. Potent CXCR4 antagonists were identified based on anti-HIV-1 activity and Ca(2+) flux inhibition that displayed good pharmacokinetics in rat and dog.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacokinetics
  • Calcium Signaling
  • Dogs
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Humans
  • Rats
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Receptors, CXCR4 / metabolism
  • Structure-Activity Relationship
  • Virus Replication / drug effects*

Substances

  • Anti-HIV Agents
  • Heterocyclic Compounds, 1-Ring
  • Receptors, CXCR4
  • mavorixafor