Document Report Card
Basic Information
ID: ALA3792364
Journal: Bioorg Med Chem Lett
Title: Identification and biological activity of 6-alkyl-substituted 3-methyl-pyridine-2-carbonyl amino dimethyl-benzoic acid EP4 antagonists.
Authors: Blanco MJ, Vetman T, Chandrasekhar S, Fisher MJ, Harvey A, Kuklish SL, Chambers M, Lin C, Mudra D, Oskins J, Wang XS, Yu XP, Warshawsky AM.
Abstract: Continued SAR optimization of a series of 3-methylpyridine-2-carbonyl amino-2,4-dimethyl-benzoic acid led to the selection of compound 4f for clinical studies. Compound 4f showed an IC50 of 123nM for inhibition of PGE2-induced TNFα reduction in an ex vivo LPS-stimulated human whole blood assay (showing >10-fold increase over clinical compound CJ-023,423). Pharmacokinetic profile, selectivity and in vivo efficacy comparing 4f to NSAID diclofenac in the monoiodoacetic acid (MIA) pain model and adjuvant induced arthritis (AIA) inflammatory model are included.
CiteXplore: 27020304