Design and synthesis of a novel, orally active, brain penetrant, tri-substituted thiophene based JNK inhibitor.

@article{Bowers2011DesignAS,
  title={Design and synthesis of a novel, orally active, brain penetrant, tri-substituted thiophene based JNK inhibitor.},
  author={Simeon Bowers and Anh P. Truong and R. Jeffrey Neitz and Martin Leon Neitzel and G. Duane Probst and Roy Kay Hom and Brian T. Peterson and Robert Anthony Galemmo and Andrei William Konradi and Hing Leung Sham and Gergley T{\'o}th and Hu Dan Pan and Nanhua H. Yao and Dean R. Artis and Elizabeth F. Brigham and Kevin P. Quinn and J. D. Sauer and Kyle A Powell and Lany Ruslim 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={2011},
  volume={21 6},
  pages={
          1838-43
        }
}
The SAR of a series of tri-substituted thiophene JNK3 inhibitors is described. By optimizing both the N-aryl acetamide region of the inhibitor and the 4-position of the thiophene we obtained single digit nanomolar compounds, such as 47, which demonstrated an in vivo effect on JNK activity when dosed orally in our kainic acid mouse model as measured by phospho-c-jun reduction. 
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