| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1368612 | Bioorganic & Medicinal Chemistry Letters | 2016 | 5 Pages |
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 123 nM 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.
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Authors
Maria-Jesus Blanco, Tatiana Vetman, Srinivasan Chandrasekhar, Matthew J. Fisher, Anita Harvey, Steven L. Kuklish, Mark Chambers, Chaohua Lin, Daniel Mudra, Jennifer Oskins, Xu-Shan Wang, Xiao-Peng Yu, Alan M. Warshawsky,