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A novel series of highly selective JNK inhibitors based on the 4-quinolone scaffold was designed and synthesized. Structure based drug design was utilized to guide the compound design as well as improvements in the physicochemical properties of the series. Compound (13c) has an IC 50 of 62/170nM for JNK1/2, excellent kinase selectivity and impressive efficacy in a rodent asthma model.
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