3-alkyl-5-aryl-1-pyrimidyl-1-pyrazole derivatives were designed and synthesised as selective inhibitors of JNK3, a target for the treatment of neurodegenerative diseases. Following previous studies, we have designed JNK3 inhibitors to reduce the molecular weight and successfully identified a lead compound that exhibits equipotent activity towards JNK3. Kinase profiling results also showed high selectivity for JNK3 among 38 kinases. Among the derivatives, the IC value of ()-2-(1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-5-(3,4-dichlorophenyl)-1-pyrazol-3-yl)acetonitrile exhibited 227 nM, showing the highest inhibitory activity against JNK3.
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| http://dx.doi.org/10.1080/14756366.2019.1705294 | DOI Listing |
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