Exploration of SAR features by modifications of thiazoleacetic acids as CRTH2 antagonists

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1638-41. doi: 10.1016/j.bmcl.2010.01.092. Epub 2010 Jan 22.

Abstract

The SAR features have been further explored for (2-benzhydryl-4-phenyl-thiazol-5-yl)acetic acids as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. The introduction of a nitrogen or a methyl substituent in the benzhydrylic position offer two alternative drugable scaffolds attractive for unsymmetrically substituted derivatives. An imidazole analogue lacks activity due to formation of a favored coplanar intramolecular hydrogen bond. The pyrimidine derivative 18 represents a potent and selective compound that will be subject to continued investigations.

MeSH terms

  • Animals
  • Benzhydryl Compounds / chemical synthesis
  • Benzhydryl Compounds / chemistry*
  • Benzhydryl Compounds / pharmacokinetics
  • Binding Sites
  • Cell Line
  • Computer Simulation
  • Humans
  • Hydrogen Bonding
  • Imidazoles / chemistry
  • Mice
  • Models, Molecular
  • Nitrogen / chemistry
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacokinetics
  • Rats
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Immunologic / metabolism
  • Receptors, Prostaglandin / antagonists & inhibitors*
  • Receptors, Prostaglandin / metabolism
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry*
  • Thiazoles / pharmacokinetics

Substances

  • Benzhydryl Compounds
  • Imidazoles
  • Pyrimidines
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • Thiazoles
  • imidazole
  • pyrimidine
  • Nitrogen
  • prostaglandin D2 receptor