Peifer, Christian published the artcile3,4-Diaryl-isoxazoles and -imidazoles as Potent Dual Inhibitors of p38α Mitogen Activated Protein Kinase and Casein Kinase 1δ, Synthetic Route of 16909-09-4, the publication is Journal of Medicinal Chemistry (2009), 52(23), 7618-7630, database is CAplus and MEDLINE.
In this study, we report on the discovery of isoxazole 1 as a potent dual inhibitor of p38α (IC50 = 0.45 μM) and CK1δ (IC50 = 0.23 μM). Because only a few effective small mol. inhibitors of CK1 have been described so far, we aimed to develop this structural class toward specific agents. Mol. modeling studies comparing p38α/CK1δ suggested an optimization strategy leading to design, synthesis, biol. characterization, and SAR of highly potent compounds including 9 (IC50 p38α = 0.006 μM; IC50 CK1δ = 1.6 μM), 13 (IC50 p38α = 2.52 μM; IC50 CK1δ = 0.033 μM), 17 (IC50 p38α = 0.019 μM; IC50 CK1δ = 0.004 μM; IC50 CK1ε = 0.073 μM), and 18 (CKP138) (IC50 p38α = 0.041 μM; IC50 CK1δ = 0.005 μM; IC50 CK1ε = 0.447 μM) possessing differentiated specificity. Selected compounds were profiled over 76 kinases and evaluation of their cellular efficacy showed 18 (CKP138) to be a highly potent and dual-specific inhibitor of CK1δ and p38α.
Journal of Medicinal Chemistry published new progress about 16909-09-4. 16909-09-4 belongs to catalysis-chemistry, auxiliary class Alkenyl,Carboxylic acid,Benzene,Ether, name is (E)-3-(2,4-Dimethoxyphenyl)acrylic acid, and the molecular formula is C11H12O4, Synthetic Route of 16909-09-4.
Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia