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

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.

Graphical abstractSAR data have been supported by key analogues of thiazoleacetic acids and modelling studies to arrive at potent and novel chemotypes of CRTH2 antagonists.Figure optionsDownload full-size imageDownload as PowerPoint slide