Design and synthesis of brain penetrant selective JNK inhibitors with improved pharmacokinetic properties for the prevention of neurodegeneration.

@article{Bowers2011DesignAS,
  title={Design and synthesis of brain penetrant selective JNK inhibitors with improved pharmacokinetic properties for the prevention of neurodegeneration.},
  author={Simeon Bowers and Anh P. Truong and R Jeffrey Neitz and Roy Kay Hom and Jennifer M. Sealy and G. Duane Probst and David A. Quincy and Brian T. Peterson and Wayman Chan and Robert Anthony Galemmo and Andrei William Konradi and Hing Leung Sham and Gergely T{\'o}th and Hu Dan Pan and May La Lin and Nanhua H. Yao and Dean R. Artis and Heather Zhang and Linda Chen and Mark Dryer and Bhushan Samant and Wes Zmolek and Karina L. Wong and Colin Lorentzen and Erich G. Goldbach and George Tonn and Kevin P. Quinn and J. D. Sauer and Sarah BeAnn Wright 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 18},
  pages={
          5521-7
        }
}
The SAR of a series of brain penetrant, trisubstituted thiophene based JNK inhibitors with improved pharmacokinetic properties is described. These compounds were designed based on information derived from metabolite identification studies which led to compounds such as 42 with lower clearance, greater brain exposure and longer half life compared to earlier analogs. 
BETA

Similar Papers

Topics from this paper.