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

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Christopher JA, Atkinson FL, Bax BD, Brown MJ, Champigny AC, Chuang TT, Jones EJ, Mosley JE, Musgrave JR

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

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

PubMed ID

19303774 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
1-(3-bromophenyl)-7-chloro-6-methoxy-3,4-dihydroisoquinoline	Mitogen-activated protein kinase 10	IC 50 (nM)	398.11	N/A	N/A	Details