2. Academic Validation
  3. Design and synthesis of disubstituted thiophene and thiazole based inhibitors of JNK

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

  • Bioorg Med Chem Lett. 2010 Dec 15;20(24):7303-7. doi: 10.1016/j.bmcl.2010.10.066.
Roy K Hom 1,  Simeon Bowers,  Jennifer M Sealy,  Anh P Truong,  Gary D Probst,  Martin L Neitzel,  R Jeffrey Neitz,  Larry Fang,  Louis Brogley,  Jing Wu,  Andrei W Konradi,  Hing L Sham,  Gergely Tóth,  Hu Pan,  Nanhua Yao,  Dean R Artis,  Kevin Quinn,  John-Michael Sauer,  Kyle Powell,  Zhao Ren,  Frédérique Bard,  Ted A Yednock,  Irene Griswold-Prenner
Affiliations

Affiliation

  • 1 Department of Chemical Sciences, Elan Pharmaceuticals, South San Francisco, CA 94080, USA. [email protected]
PMID: 21071223 DOI: 10.1016/j.bmcl.2010.10.066
Abstract

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(50)=77 nM and retained the excellent broad kinase selectivity observed for the series.

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