1229571-92-9Relevant academic research and scientific papers
An optimized and versatile synthesis to pyridinylimidazole-type p38α mitogen activated protein kinase inhibitors
El-Gokha, Ahmed,Laufer, Stefan A.,Koch, Pierre
, p. 10699 - 10704 (2015/11/17)
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.
Unexpected reaction of 2-alkylsulfanylimidazoles to imidazol-2-ones: Pyridinylimidazol-2-ones as novel potent P38α mitogen-activated protein kinase inhibitors
Koch, Pierre,Laufer, Stefan
scheme or table, p. 4798 - 4802 (2010/10/03)
While optimizing the synthesis of 2-alkylsulfanyl-5-(2-aminopyridin-4-yl) imidazoles, we identified an unexpected reaction to pyridinylimidazol-2-ones. 2-Alkylsulfanylimidazoles, bearing a 2-hydroxyethyl or a 2,3-dihydroxypropyl moiety at the imidazole C2-S position, were converted by heating into imidazol-2-ones. These imidazol-2-ones were tested for their ability to inhibit p38α MAP kinase and LPS-stimulated TNF-α release in HWB. Introduction of an amino moiety at the pyridine C2 position led to compounds showing potent enzyme inhibitory activity with double-digit nanomolar IC 50 values (5a: IC50 = 23 nM).
