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Bioorg Med Chem Lett. 2009 May 15;19(10):2891-5. doi: 10.1016/j.bmcl.2009.03.043. Epub 2009 Mar 17.

Structure-based design and parallel synthesis of N-benzyl isatin oximes as JNK3 MAP kinase inhibitors.

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  • 1Vertex Pharmaceuticals Incorporated, Cambridge, MA 02139, United States.


A series of N-benzylated isatin oximes were developed as inhibitors of the mitogen-activated kinase, JNK3. X-ray crystallographic structures aided in the design and synthesis of novel, selective compounds, that inhibit JNK3, but not p38 MAP kinase and provided key insights into understanding the behavior of gatekeeper residue methionine-146 in determining target selectivity for this series.

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