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Synthesis and SAR of novel quinazolines as potent and brain-penetrant c-jun N-terminal kinase (JNK) inhibitors |
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| Authors: | He Yuanjun Kamenecka Theodore M Shin Youseung Song Xinyi Jiang Rong Noel Romain Duckett Derek Chen Weimin Ling Yuan Yuan Cameron Michael D Lin Li Khan Susan Koenig Marcel LoGrasso Philip V |
| Institution: | Department of Molecular Therapeutics and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA |
| Abstract: | Quinazoline 3 was discovered as a novel c-jun N-terminal kinase (JNK) inhibitor with good brain penetration and pharmacokinetic (PK) properties. A number of analogs which were potent both in the biochemical and cellular assays were discovered. Quinazoline 13a was found to be a potent JNK3 inhibitor (IC50 = 40 nM), with >500-fold selectivity over p38, and had good PK and brain penetration properties. With these properties, 13a is considered a potential candidate for in vivo evaluation. |
| Keywords: | JNK Quinazoline Inhibitors |
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