3OXI

Design and Synthesis of Disubstituted Thiophene and Thiazole Based Inhibitors of JNK for the Treatment of Neurodegenerative Diseases

Summary for 3OXI

• Entry DOI: 10.2210/pdb3oxi/pdb
• Descriptor: Mitogen-activated protein kinase 10, Mitogen-activated protein kinase 8 interacting protein 1, methyl 3-[(thiophen-2-ylacetyl)amino]thiophene-2-carboxylate, ... (4 entities in total)
• Functional Keywords: jnk inhibitors, neurodegenerative diseases, kinase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P53779
• Total number of polymer chains: 2
• Total formula weight: 43269.13

Authors

Hom, R.K.,Bowers, S.,Sealy, J.,Truong, A.,Probst, G.D.,Neitzel, M.,Neitz, J.,Fang, L.,Brogley, L.,Wu, J.,Konradi, A.W.,Sham, H.,Toth, G.,Pan, H.,Yao, N.,Artis, D.R. (deposition date: 2010-09-21, release date: 2011-05-04, Last modification date: 2024-02-21)

Primary citation

Hom, R.K.,Bowers, S.,Sealy, J.M.,Truong, A.P.,Probst, G.D.,Neitzel, M.L.,Neitz, R.J.,Fang, L.,Brogley, L.,Wu, J.,Konradi, A.W.,Sham, H.L.,Toth, G.,Pan, H.,Yao, N.,Artis, D.R.,Quinn, K.,Sauer, J.M.,Powell, K.,Ren, Z.,Bard, F.,Yednock, T.A.,Griswold-Prenner, I.
Design and synthesis of disubstituted thiophene and thiazole based inhibitors of JNK.
Bioorg.Med.Chem.Lett., 20:7303-7307, 2010

PubMed Abstract: 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.

PubMed: 21071223
DOI: 10.1016/j.bmcl.2010.10.066

Experimental method

X-RAY DIFFRACTION (2.2 Å)