jm060657g_si_002.pdf (148.29 kB)
Novel Selective Orally Active CRTH2 Antagonists for Allergic Inflammation Developed from in Silico Derived Hits
journal contribution
posted on 2006-11-16, 00:00 authored by Trond Ulven, Jean-Marie Receveur, Marie Grimstrup, Øystein Rist, Thomas M. Frimurer, Lars-Ole Gerlach, Jesper Mosolff Mathiesen, Evi Kostenis, Lena Uller, Thomas HögbergHits 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.