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Design and synthesis of disubstituted thiophene and thiazole based inhibitors of JNK

Journal Article · · Bioorg. Med. Chem. Lett.

From high throughput screening, we discovered compound 1, the prototype for a series of disubstituted thiophene inhibitors of JNK which is selective towards closely related MAP kinases p38 and Erk2. Herein we describe the evolution of these compounds to a novel class of thiophene and thiazole JNK inhibitors that retain favorable solubility, permeability, and P-gp properties for development as CNS agents for treatment of neurodegeneration. Compound 61 demonstrated JNK3 IC{sub 50} = 77 nM and retained the excellent broad kinase selectivity observed for the series.

Research Organization:
Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
Sponsoring Organization:
USDOE Office of Science (SC)
OSTI ID:
1026552
Journal Information:
Bioorg. Med. Chem. Lett., Journal Name: Bioorg. Med. Chem. Lett. Journal Issue: (24) ; 12, 2010 Vol. 20
Country of Publication:
United States
Language:
ENGLISH

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