PDB 3RTP deposited: 2011-05-03 modified: 2013-05-08
Title Design and synthesis of brain penetrant selective JNK inhibitors with improved pharmacokinetic properties for the prevention of neurodegeneration
Authors Artis, D.R., Bard, F., Bowers, S., Chan, W., Chen, L., Dryer, M., Galemmo, R.A., Goldbach, E., Griswold-Prenner, I., Hom, R.K., Jeffrey Neitz, R., Konradi, A.W., Lin, M., Lorentzen, C., Pan, H., Peterson, B., Powell, K., Probst, G.D., Quincy, D., Quinn, K.P., Ren, Z., Ruslim, L., Samant, B., Sauer, J.M., Sealy, J.M., Sham, H.L., Tonn, G., Toth, G., Truong, A.P., Wong, K., Wright, S., Yao, N., Yednock, T.A., Zhang, H., Zmolek, W.
Structure factors resolution 2.4 rfactor 0.23532 rfree 0.30884
DPI 2.25 theoretical min: 0.39

The SAR of a series of brain penetrant, trisubstituted thiophene based JNK inhibitors with improved pharmacokinetic properties is described. These compounds were designed based on information derived from metabolite identification studies which led to compounds such as 42 with lower clearance, greater brain exposure and longer half life compared to earlier analogs.

Bioorg.Med.Chem.Lett. 2011 Sep; 21(18):5521-5527 doi:10.1016/j.bmcl.2011.06.100

Cross References
Database source Identifier Description
ChEMBL Document CHEMBL1821697
PubMed 21813278 BMCLE8
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
3RTP/0 3RTP 0 monomer 0 1 1 2487