Optimization of the heterocyclic core of the quinazolinone-derived CXCR3 antagonists

Bioorg Med Chem Lett. 2008 Jan 15;18(2):688-93. doi: 10.1016/j.bmcl.2007.11.060. Epub 2007 Nov 21.

Abstract

A series of six-six and six-five fused heterocyclic CXCR3 antagonists has been synthesized and their activities evaluated in an [(125)I]-IP-10 displacement assay and an ITAC mediated in vitro cell migration assay. The pharmacokinetic properties of several top compounds have also been studied. This effort led to the discovery of compounds with increased potency and improved pharmacokinetic properties that could serve as useful tools to study the role of the CXCR3 receptor in vivo.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Heterocyclic Compounds / pharmacology*
  • Humans
  • Quinazolinones / pharmacokinetics
  • Quinazolinones / pharmacology*
  • Rats
  • Receptors, CXCR3 / antagonists & inhibitors*
  • Stereoisomerism

Substances

  • CXCR3 protein, human
  • Heterocyclic Compounds
  • Quinazolinones
  • Receptors, CXCR3