SAR of benzoylpyridines and benzophenones as p38alpha MAP kinase inhibitors with oral activity.
作者信息
Revesz Laszlo, Blum Ernst, Di Padova Franco E, Buhl Thomas, Feifel Roland, Gram Hermann, Hiestand Peter, Manning Ute, Rucklin Gerard
机构信息
Novartis Institutes for BioMedical Research, Arthritis and Bone Metabolism, CH-4002 Basel, Switzerland.
出版信息
Bioorg Med Chem Lett. 2004 Jul 5;14(13):3601-5. doi: 10.1016/j.bmcl.2004.03.111.
PMID:15177483
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.
摘要
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