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

Summary, in English

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.

• Författare: Trond Ulven; Jean-Marie Receveur; Marie Grimstrup; Oystein Rist; Thomas M Frimurer; Lars-Ole Gerlach; Jesper Mosolff Mathiesen; Evi Kostenis; Lena Uller; Thomas Hogberg
• Avdelning/ar: Lungbiologi
• Publiceringsår: 2006
• Språk: Engelska
• Sidor: 6638-6641
• Publikation/Tidskrift/Serie: Journal of Medicinal Chemistry
• Volym: 49
• Issue: 23
• Länkar: http://dx.doi.org/10.1021/jm060657g
• Dokumenttyp: Artikel i tidskrift
• Förlag: The American Chemical Society (ACS)
• Ämne: Cell and Molecular Biology
• Status: Published
• Forskningsgrupp: Lung Biology
• ISBN/ISSN/Övrigt: ISSN: 1520-4804