Document Report Card

ID: ALA1137324

Journal: J Med Chem

Title: Novel selective orally active CRTH2 antagonists for allergic inflammation developed from in silico derived hits.

Authors: Ulven T, Receveur JM, Grimstrup M, Rist Ø, Frimurer TM, Gerlach LO, Mathiesen JM, Kostenis E, Uller L, Högberg T.

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.

CiteXplore: 17154491

DOI: 10.1021/jm060657g