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Design and synthesis of brain penetrant selective JNK inhibitors with improved pharmacokinetic properties for the prevention of neurodegeneration |
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| Authors: | Bowers Simeon Truong Anh P Jeffrey Neitz R Hom Roy K Sealy Jennifer M Probst Gary D Quincy David Peterson Brian Chan Wayman Galemmo Robert A Konradi Andrei W Sham Hing L Tóth Gergely Pan Hu Lin May Yao Nanhua Artis Dean R Zhang Heather Chen Linda Dryer Mark Samant Bhushan Zmolek Wes Wong Karina Lorentzen Colin Goldbach Erich Tonn George Quinn Kevin P Sauer John-Michael Wright Sarah Powell Kyle Ruslim Lany Ren Zhao Bard Frédérique Yednock Ted A Griswold-Prenner Irene |
| Institution: | Department of Chemical Sciences, Elan Pharmaceuticals, 180 Oyster Point Boulevard, South San Francisco, CA 94080, United States. simeon.bowers@elan.com |
| Abstract: | 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. |
| Keywords: | c-Jun N-terminal kinase inhibitor JNK Neurodegeneration Trisubstituted thiophene |
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