Discovery of novel quinolinone adenosine A2B antagonists

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) which exhibited potent activity in a cAMP accumulation assay (5.1 nM) and an IL-8 release assay (0.4 nM).

Graphical abstractThe synthesis and SAR of a novel series of A2B receptor antagonists are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide