Discovery of novel quinolinone adenosine A_2B antagonists

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• 作者：Brian F. McGuinness ; Koc-Kan Ho ; Tara M. Stauffer ; Laura L. Rokosz ; Neelima Mannava ; Steven G. Kultgen ; Kurt Saionz ; Anthony Klon ; Weiqing Chen ; Hema Desai ; W. Lynn Rogers ; Maria Webb ; Juxing Yin ; Yan
• 关键词：A_2B receptor ; Adenosine ; Antagonist ; Combinatorial chemistry ; Quinolinone
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：15 December 2010
• 年：2010
• 卷：20
• 期：24
• 页码：7414-7420
• 全文大小：1718 K

文摘

A novel series of quinolinone-based adenosine A_2B receptor antagonists was identified via high throughput screening of an encoded combinatorial compound collection. Synthesis and assay of a series of analogs highlighted essential structural features of the initial hit. Optimization resulted in an A_2B antagonist (2i) which exhibited potent activity in a cAMP accumulation assay (5.1 nM) and an IL-8 release assay (0.4 nM).