PDB 3PTG deposited: 2010-12-02 modified: 2011-03-23
Title Design and Synthesis of a Novel, Orally Efficacious Tri-substituted Thiophene Based JNK Inhibitor
Authors Artis, D.R., Bard, F., Bowers, S., Brigham, E.F., Galemmo, R.A., Griswold-Prenner, I., Hom, R.K., Konradi, A.W., Neitzel, M., Neitz, R.J., Pan, H., Peterson, B., Powell, K., Probst, G.D., Quinn, K.P., Ren, Z., Ruslim, L., Sauer, J.M., Sham, H.L., Toth, G., Truong, A.P., Yao, N., Yednock, T.A.
Structure factors resolution 2.43 rfactor 0.24384 rfree 0.31597
DPI 1.02 theoretical min: 0.41

The SAR of a series of tri-substituted thiophene JNK3 inhibitors is described. By optimizing both the N-aryl acetamide region of the inhibitor and the 4-position of the thiophene we obtained single digit nanomolar compounds, such as 47, which demonstrated an in vivo effect on JNK activity when dosed orally in our kainic acid mouse model as measured by phospho-c-jun reduction.

Bioorg.Med.Chem.Lett. 2011 Mar; 21(6):1838-1843 doi:10.1016/j.bmcl.2011.01.046

Cross References
Database source Identifier Description
ChEMBL Document CHEMBL1681717
PubMed 21316234 BMCLE8
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
3PTG/1 3PTG 1 dimer 0 2 1 2561