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

@article{Hom2010DesignAS,
  title={Design and synthesis of disubstituted thiophene and thiazole based inhibitors of JNK.},
  author={Roy Kay Hom and Simeon Bowers and Jennifer M. Sealy and Anh P. Truong and G. Duane Probst and Martin Leon Neitzel and R. Jeffrey Neitz and Larry Yun Fang and Louis Brogley and Jing Jiang Wu and Andrei William Konradi and Hing Leung Sham and Gergely T{\'o}th and Hu Dan Pan and Nanhua H. Yao and Dean R. Artis and Kevin P. Quinn and J. D. Sauer and Kyle A Powell and Zhao Hua Ren and Fr{\'e}d{\'e}rique Bard and Ted A. Yednock and Irene Griswold-Prenner},
  journal={Bioorganic & medicinal chemistry letters},
  year={2010},
  volume={20 24},
  pages={
          7303-7
        }
}
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… CONTINUE READING
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