Related Experiment Video
Updated: Apr 4, 2026
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
An optimized and versatile synthesis to pyridinylimidazole-type p38α mitogen activated protein kinase inhibitors
Ahmed El-Gokha1, Stefan A Laufer2, Pierre Koch3
1Institute of Pharmaceutical Sciences, Department of Medicinal and Pharmaceutical Chemistry, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany. pierre.koch@uni-tuebingen.de and Menofia University, Chemistry Department, Faculty of Science, Menofia, Egypt.
Abstract:
An optimized strategy for the synthesis of the potent p38α mitogen-activated protein kinase inhibitors 2-(2-hydroxyethylsulfanyl)-4-(4-fluorophenyl)-5-(2-aminopyridin-4-yl)imidazole (3) and 2-(2,3-dihydroxypropylsulfanyl)-4-(4-fluorophenyl)-5-(2-aminopyridin-4-yl)imidazole (4) starting from 2-fluoro-4-methylpyridine is reported. In contrast to a previously published synthesis starting from 2-bromo-4-methylpyridine, the overall yield could be increased from 3.6% to 29.4%. Moreover, this strategy avoids the use of palladium as a catalyst and is more diverse and versatile. Using this optimized protocol, both enantiomers of potent inhibitor 3 were synthesized. Biological data demonstrated that the (S)-enantiomer is the two times more potent eutomer.
