Small‐molecule AT2 receptor agonists

Abstract The discovery of the first selective, small‐molecule ATR receptor (AT2R) agonist compound 21 (C21) ( 8 ) that is now extensively studied in a large variety of in vitro and in vivo models is described. The sulfonylcarbamate derivative 8 , encompassing a phenylthiofen scaffold is the drug‐like agonist with the highest affinity for the AT2R reported to date ( K i = 0.4 nM). Structure‐activity relationships (SAR), regarding different biaryl scaffolds and functional groups attached to these scaffolds and with a particular focus on the impact of various para substituents displacing the methylene imidazole group of 8 , are discussed. Furthermore, the consequences of migration of the methylene imidazole group and presumed structural requirements for ligands that are aimed as AT2R agonists (e.g. 8 ) or AT2R antagonists (e.g. 9 ), respectively, are briefly addressed. A summary of the pharmacological actions of C21 ( 8 ) is also presented.