Title of article
N-(3-Cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amides as potent, selective, inhibitors of JNK2 and JNK3
Author/Authors
Richard M. Angell، نويسنده , , Francis L. Atkinson، نويسنده , , Murray J. Brown، نويسنده , , Tsu Tshen Chuang، نويسنده , , John A. Christopher، نويسنده , , Maria Cichy-Knight، نويسنده , , Allison K. Dunn، نويسنده , , Kendra E. Hightower، نويسنده , , Susanna Malkakorpi، نويسنده , , James R. Musgrave، نويسنده , , Margarete Neu، نويسنده , , Paul Rowland، نويسنده , , Robyn L. Shea، نويسنده , , Jeffery L. Smith، نويسنده , , Donald O. Somers، نويسنده , , Sonia A. Thomas، نويسنده , , Gladstone Thompson، نويسنده , , Ruolan Wang، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2007
Pages
6
From page
1296
To page
1301
Abstract
The identification and exploration of a novel, potent and selective series of N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amide inhibitors of JNK2 and JNK3 kinases is described. Compounds 5a and 11a were identified as potent inhibitors of JNK3 (pIC50 6.7 and 6.6, respectively), with essentially equal potency against JNK2 (pIC50 6.5). Selectivity within the mitogen-activated protein kinase (MAPK) family, against JNK1, p38α and ERK2, was observed for the series. X-ray crystallography of 5e and 8a in JNK3 revealed a unique binding mode, with the 3-cyano substituent forming an H-bond acceptor interaction with the hinge region of the ATP-binding site.
Keywords
JNK , JNK3 , kinase , MAPK , inhibitor , Selective
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2007
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
797838
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