Discovery of novel quinolinone adenosine A2B antagonists

Published in: Journal, Article, Volume : 20, Issue : 24, Pages : 7414-7420

DOI : 10.1016/j.bmcl.2010.10.030

Author : McGuinness, Brian F.; Ho, Koc-Kan; Stauffer, Tara M.; Rokosz, Laura L.; Mannava, Neelima; Kultgen, Steven G.; Saionz, Kurt; Klon, Anthony; Chen, Weiqing; Desai, Hema; Rogers, W. Lynn; Webb, Maria; Yin, Juxing; Jiang, Yan; Li, Tailong; Yan, Hao; Jing, Konghua; Zhang, Shengting; Majumdar, Kanak Kanti; Srivastava, Vikash; Saha, Samiran

Abstract : A novel series of quinolinone-based adenosine A2B 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 A2B antagonist (2i, I) which exhibited potent activity in a cAMP accumulation assay (5.1 nM) and an IL-8 release assay (0.4 nM).