Discovery and optimization of a series of quinazolinone-derived antagonists of CXCR3

Bioorg Med Chem Lett. 2007 Jun 15;17(12):3339-43. doi: 10.1016/j.bmcl.2007.03.106. Epub 2007 Apr 6.

Abstract

A series of quinazolinone-derived inhibitors of the CXCR3 receptor have been synthesized and their affinity for the receptor evaluated. Compounds were evaluated in a (125)I-IP10 displacement assay and in in vitro cell migration assays to IP10, ITAC, and MIG using human peripheral blood mononuclear cells.

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cell Movement / drug effects*
  • Cell Movement / physiology
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Iodine Radioisotopes
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism
  • Mice
  • Models, Chemical
  • Oligopeptides / metabolism
  • Quinazolinones / chemical synthesis
  • Quinazolinones / pharmacology*
  • Radioligand Assay
  • Receptors, CXCR3
  • Receptors, Chemokine / antagonists & inhibitors*
  • Receptors, Cytokine / metabolism
  • Structure-Activity Relationship

Substances

  • CXCR3 protein, human
  • Cxcr3 protein, mouse
  • IP10-Mig receptor
  • ITAC peptide
  • Intercellular Signaling Peptides and Proteins
  • Iodine Radioisotopes
  • Oligopeptides
  • Quinazolinones
  • Receptors, CXCR3
  • Receptors, Chemokine
  • Receptors, Cytokine