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Bioorg Med Chem Lett. 2009 Apr 15;19(8):2230-4. doi: 10.1016/j.bmcl.2009.02.098. Epub 2009 Feb 28.

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

Author information

1
GlaxoSmithKline R&D, Medicines Research Centre, Stevenage, Hertfordshire, UK. john@christopher257.fsnet.co.uk

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 p38alpha and ERK2. X-ray crystallography of 16 reveals a highly unusual binding mode where an H-bond acceptor interaction with the hinge region is made by a chloro substituent.

PMID:
19303774
DOI:
10.1016/j.bmcl.2009.02.098
[Indexed for MEDLINE]

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