N-(3-Cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amides as potent, selective, inhibitors of JNK2 and JNK3
| Autor: | Margarete Neu, Donald O. Somers, Gladstone Thompson, Richard Martyn Angell, Kendra E. Hightower, Jeffery L. Smith, Maria Cichy-Knight, Tsu Tshen Chuang, Ruolan Wang, Murray J. B. Brown, Sonia Thomas, Allison K. Dunn, Robyn L. Shea, Susanna Malkakorpi, James R. Musgrave, Francis Louis Atkinson, John A. Christopher, Paul Rowland |
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| Rok vydání: | 2006 |
| Předmět: |
Nitrile
Stereochemistry medicine.drug_class Clinical Biochemistry Substituent Pharmaceutical Science Carboxamide Crystallography X-Ray Biochemistry Chemical synthesis chemistry.chemical_compound Structure-Activity Relationship Mitogen-Activated Protein Kinase 10 Amide Drug Discovery medicine Benzene Derivatives Structure–activity relationship Humans Mitogen-Activated Protein Kinase 9 Binding site Molecular Biology Binding Sites Chemistry Kinase Organic Chemistry Amides Molecular Medicine |
| Zdroj: | Bioorganicmedicinal chemistry letters. 17(5) |
| ISSN: | 0960-894X |
| Popis: | 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, p38alpha 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. |
| Databáze: | OpenAIRE |
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