SAR of benzoylpyridines and benzophenones as p38alpha MAP kinase inhibitors with oral activity |
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| Authors: | Revesz Laszlo Blum Ernst Di Padova Franco E Buhl Thomas Feifel Roland Gram Hermann Hiestand Peter Manning Ute Rucklin Gerard |
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| Institution: | Novartis Institutes for BioMedical Research, Arthritis and Bone Metabolism, CH-4002 Basel, Switzerland. laszlo.revesz@pharma.novartis.com |
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| Abstract: | Benzoylpyridines and benzophenones were synthesized and evaluated in vitro as p38alpha inhibitors and in vivo in several models of rheumatoid arthritis. Oral activity was found to depend upon substitution: 1,1-dimethylpropynylamine substituted benzophenone 10b (IC50: 14 nM) and pyridinoyl substituted benzimidazole 17b (IC50: 21 nM) showed highest efficacy and selectivity with ED50s of 9.5 and 8.6 mg/kg p.o. in CIA. |
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