| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1372113 | Bioorganic & Medicinal Chemistry Letters | 2010 | 5 Pages |
Structure–activity relationships have been established by exploring the eastern and western side of 5-thiazolyleacetic acids as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. Benzhydryl motifs in the 2-position of the thiazole was found to be most advantageous. The 4-thiazole position should either carry 3- or 4-fluorophenyl rings or a 4-pyridyl suitably substituted in the flanking 2-position. Several compounds with single digit nanomolar binding affinity and full antagonistic efficacy for human CRTH2 receptor were obtained. The compound series display a good PK profile and selectivity over a large number of other targets.
Graphical abstractSAR has been established by exploring the eastern and western side of 5-thiazoleacetic acids supported by modeling and docking studies.Figure optionsDownload full-size imageDownload as PowerPoint slide
