2-Mercaptoimidazoles, a new class of potent CCR2 antagonists

Bioorg Med Chem Lett. 2005 Feb 1;15(3):497-500. doi: 10.1016/j.bmcl.2004.11.064.

Abstract

We describe the synthesis and SAR of a new class of CCR2 antagonists based on 2-mercaptoimidazole scaffold. The initial lead 1a was optimized to the 3,4-disubstituted analogues 1p-(S) and 1q-(S), which have IC(50) values in the MCP-1 induced Ca-flux below 0.01 microM.

MeSH terms

  • Calcium Signaling / drug effects
  • Cell Line
  • Chemokine CCL2 / pharmacology
  • Ethylenethiourea* / analogs & derivatives*
  • Ethylenethiourea* / chemical synthesis*
  • Ethylenethiourea* / pharmacology*
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / pharmacology
  • Inhibitory Concentration 50
  • Receptors, CCR2
  • Receptors, Chemokine / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • CCL2 protein, human
  • CCR2 protein, human
  • Chemokine CCL2
  • Imidazoles
  • Receptors, CCR2
  • Receptors, Chemokine
  • Ethylenethiourea
  • 2-mercaptoimidazole