Synthesis of Potent Bicyclic Bisarylimidazole c-Jun N-Terminal Kinase Inhibitors by Catalytic C-H Bond Activation

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• 作者：Jason C. Rech ; Michihisa Yato ; Derek Duckett ; Brian Ember ; Philip V. LoGrasso ; Robert G. Bergman ; Jonathan A. Ellman
• 刊名：Journal of the American Chemical Society
• 出版年：2007
• 出版时间：January 24, 2007
• 年：2007
• 卷：129
• 期：3
• 页码：490 - 491
• 全文大小：40K
• 年卷期：v.129,no.3(January 24, 2007)
• ISSN：1520-5126

文摘

The efficient preparation of the privileged bicyclic bisarylimidazole kinase inhibitor scaffold was accomplished using rhodium-catalyzed C-H activation and intramolecular alkylation. The key C-H activation/alkylation step represents one of the first evaluations of diastereocontrol in catalyzed C-H activation/olefin alkylation processes. Several inhibitors of JNK3 were prepared using this sequence, with the most potent inhibitor having an IC₅₀ value of 1.6 nM.