3OXI

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

3OXI の概要

• エントリーDOI: 10.2210/pdb3oxi/pdb
• 分子名称: 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)
• 機能のキーワード: jnk inhibitors, neurodegenerative diseases, kinase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P53779
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 43269.13

構造登録者

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. (登録日: 2010-09-21, 公開日: 2011-05-04, 最終更新日: 2024-02-21)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.2 Å)