19075-64-0Relevant academic research and scientific papers
Discovery of potent, selective, and orally bioavailable alkynylphenoxyacetic acid CRTH2 (DP2) receptor antagonists for the treatment of allergic inflammatory diseases
Crosignani, Stefano,Prêtre, Adeline,Jorand-Lebrun, Catherine,Fraboulet, Ga?le,Seenisamy, Jeyaprakashnarayanan,Augustine, John Kallikat,Missotten, Marc,Humbert, Yves,Cleva, Christophe,Abla, Nada,Daff, Hamina,Schott, Olivier,Schneider, Manfred,Burgat-Charvillon, Fabienne,Rivron, Delphine,Hamernig, Ingrid,Arrighi, Jean-Fran?ois,Gaudet, Marilène,Zimmerli, Simone C.,Juillard, Pierre,Johnson, Zoe
supporting information; experimental part, p. 7299 - 7317 (2011/12/15)
New phenoxyacetic acid antagonists of CRTH2 are described. Following the discovery of a hit compound by a focused screening, high protein binding was identified as its main weakness. Optimization aimed at reducing serum protein binding led to the identification of several compounds that showed not only excellent affinities for the receptor (41 compounds with Ki 50 100 nM; PGD2-induced eosinophil shape change). Additional optimization of the PK characteristics led to the identification of several compounds suitable for in vivo testing. Of these, 19k and 19s were tested in two different pharmacological models (acute FITC-mediated contact hypersensitivity and ovalbumin-induced eosinophilia models) and found to be active after oral dosing (10 and 30 mg/kg).
PHENOXY ACETIC ACID DERIVATIVES
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Page/Page column 87, (2010/09/03)
The present invention provides phenoxyacetic acid derivatives of Formula (I) for the treatment of CRTH2 related disorders and disease selected from asthma, atopic dermatitis and inflammatory dermatoses.
