Novel selective orally active CRTH2 antagonists for allergic inflammation developed from in silico derived hits
- J Med Chem. 2006 Nov 16;49(23):6638-41. doi: 10.1021/jm060657g.
Affiliations
- 1. 7TM Pharma, Fremtidsvej 3, DK-2970 Hørsholm, Denmark. [email protected]
PMID: 17154491
DOI: 10.1021/jm060657g
Abstract
Hits from an in silico derived focused library for CRTH2 were transformed into highly selective antagonists with favorable ADME properties. Oral administration of 4-bromo-2-(1-phenyl-1H-pyrazole-4-carbonyl)phenoxyacetic acid (19) inhibited peribronchial eosinophilia and mucus cell hyperplasia in a mouse model of allergic asthma, supporting the therapeutic potential of this novel compound class. In addition, this selective pharmacological tool compound provides further evidence for CRTH2 as a relevant therapeutic target for treatment of Th2- and eosinophil-related inflammation.