1-Aryl-3, 4-dihydroisoquinoline inhibitors of JNK3

…, TT Chuang, EJ Jones, JE Mosley, JR Musgrave

Index: Christopher, John A.; Atkinson, Francis L.; Bax, Benjamin D.; Brown, Murray J.B.; Champigny, Aurelie C.; Chuang, Tsu Tshen; Jones, Emma J.; Mosley, Julie E.; Musgrave, James R. Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 8 p. 2230 - 2234

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Citation Number: 25

Abstract

A series of 1-aryl-3, 4-dihydroisoquinoline inhibitors of JNK3 are described. Compounds 20 and 24 are the most potent inhibitors (pIC50 7.3 and 6.9, respectively in a radiometric filter binding assay), with 10-and 1000-fold selectivity over JNK2 and JNK1, respectively, and selectivity within the wider mitogen-activated protein kinase (MAPK) family against p38α and ERK2. X-ray crystallography of 16 reveals a highly unusual binding mode where an H- ...