Discovery of potent and selective bicyclic A2B adenosine receptor antagonists via bioisosteric amide replacement

Several new potent and selective A2B adenosine receptor antagonists have been prepared in which the aryl–amide moiety of the lead series, exemplified by 1a, has been replaced by bioisosteric bicyclic moieties. Although the majority of compounds had generally improved microsomal stability as compared to 1a, this was not translated into overall improvements in the pharmacokinetic profiles of a representative set of compounds.

Graphical abstractSeveral novel, potent and selective A2B adenosine receptor antagonists have been prepared in which the aryl-amide moiety of the lead series 1 was replaced by various bioisosteric bicyclic moieties.Figure optionsDownload full-size imageDownload as PowerPoint slide