Core exploration in optimization of chemokine receptor CCR4 antagonists

Bioorg Med Chem Lett. 2007 Feb 1;17(3):679-82. doi: 10.1016/j.bmcl.2006.10.091. Epub 2006 Nov 2.

Abstract

The design, synthesis, and SAR studies of 'core' variations led to identification of novel, selective, and potent small molecule antagonist (22) of the CC chemokine receptor-4 (CCR4) with improved in vitro activity and liability profile. Compound 22 was efficacious in a murine allergic inflammation model (ED50 approximately 10 mg/kg).

MeSH terms

  • Animals
  • Benzyl Compounds / chemical synthesis
  • Benzyl Compounds / pharmacology
  • Cell Line
  • Chemotaxis / drug effects
  • Dose-Response Relationship, Drug
  • Indicators and Reagents
  • Mice
  • Ovalbumin
  • Pneumonia / chemically induced
  • Pneumonia / drug therapy
  • Quinolines / chemical synthesis
  • Quinolines / pharmacology
  • Receptors, CCR4
  • Receptors, Chemokine / antagonists & inhibitors*
  • Respiratory Hypersensitivity / drug therapy
  • Respiratory Hypersensitivity / pathology
  • Structure-Activity Relationship

Substances

  • Benzyl Compounds
  • Ccr4 protein, mouse
  • Indicators and Reagents
  • Quinolines
  • Receptors, CCR4
  • Receptors, Chemokine
  • Ovalbumin