Novel Tricyclic Inhibitors of IκB Kinase

详细信息    查看全文

• 作者：James Kempson*^† ; ; Steven H. Spergel^† ; ; Junqing Guo^† ; ; Claude Quesnelle^† ; ; Patrice Gill^† ; ; Dominique Belanger^†
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：April 9, 2009
• 年：2009
• 卷：52
• 期：7
• 页码：1994-2005
• 全文大小：274K
• 年卷期：v.52,no.7(April 9, 2009)
• ISSN：1520-4804

文摘

The design and synthesis of a novel series of oxazole-, thiazole-, and imidazole-based inhibitors of IκB kinase (IKK) are reported. Biological activity was improved compared to the pyrazolopurine lead, and the expedient synthesis of the new tricyclic systems allowed for efficient exploration of structure−activity relationships. This, combined with an iterative rat cassette dosing strategy, was used to identify compounds with improved pharmacokinetic (PK) profiles to advance for in vivo evaluation.