PDB 3OXI deposited: 2010-09-21 modified: 2012-02-29
Title Design and Synthesis of Disubstituted Thiophene and Thiazole Based Inhibitors of JNK for the Treatment of Neurodegenerative Diseases
Authors Artis, D.R., Bard, F., Bowers, S., Brogley, L., Fang, L., Griswold-Prenner, I., Hom, R.K., Konradi, A.W., Neitzel, M.L., Neitz, R.J., Pan, H., Powell, K., Probst, G.D., Quinn, K., Ren, Z., Sauer, J.M., Sealy, J.M., Sham, H.L., Toth, G., Truong, A.P., Wu, J., Yao, N., Yednock, T.A.
Structure factors resolution 2.2 rfactor 0.22933 rfree 0.27545
DPI 0.65 theoretical min: 0.28

From high throughput screening, we discovered compound 1, the prototype for a series of disubstituted thiophene inhibitors of JNK which is selective towards closely related MAP kinases p38 and Erk2. Herein we describe the evolution of these compounds to a novel class of thiophene and thiazole JNK inhibitors that retain favorable solubility, permeability, and P-gp properties for development as CNS agents for treatment of neurodegeneration. Compound 61 demonstrated JNK3 IC(50)=77 nM and retained the excellent broad kinase selectivity observed for the series.

Bioorg.Med.Chem.Lett. 2010 Dec; 20(24):7303-7307 doi:10.1016/j.bmcl.2010.10.066

Cross References
Database source Identifier Description
ChEMBL Document CHEMBL1287787
PubMed 21071223 BMCLE8
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
3OXI/1 3OXI 1 dimer 0 2 2 2559