0000000001313687
AUTHOR
Frank M. Boeckler
Structural Optimization of a Pyridinylimidazole Scaffold: Shifting the Selectivity from p38α Mitogen-Activated Protein Kinase to c-Jun N-Terminal Kinase 3
Starting from known p38α mitogen-activated protein kinase (MAPK) inhibitors, a series of inhibitors of the c-Jun N-terminal kinase (JNK) 3 was obtained. Altering the substitution pattern of the pyridinylimidazole scaffold proved to be effective in shifting the inhibitory activity from the original target p38α MAPK to the closely related JNK3. In particular, a significant improvement for JNK3 selectivity could be achieved by addressing the hydrophobic region I with a small methyl group. Furthermore, additional structural modifications permitted to explore structure–activity relationships. The most potent inhibitor 4-(4-methyl-2-(methylthio)-1H-imidazol-5-yl)-N-(4-morpholinophenyl)pyridin-2-a…
CCDC 1824231: Experimental Crystal Structure Determination
Related Article: Francesco Ansideri, Joana T. Macedo, Michael Eitel, Ahmed El-Gokha, Dhafer S. Zinad, Camilla Scarpellini, Mark Kudolo, Dieter Schollmeyer, Frank M. Boeckler, Bärbel S. Blaum, Stefan A. Laufer, and Pierre Koch|2018|ACS Omega|3|7809|doi:10.1021/acsomega.8b00668