Discovery of Heteroaryl Urea Isosteres for Formyl Peptide Receptor 2 Agonists

Formyl peptide receptor 2 (FPR2) agonists have shown efficacy in inflammatory-driven animal disease models and have the potential to treat a range of diseases. Many reported synthetic agonists contain a phenyl­urea, which appears to be necessary for activity in the reported chemotypes. We set out to find isosteres for the phenyl­urea and focused our efforts on heteroaryl rings. The wide range of potencies with heterocyclic isosteres demonstrates how electronic effects of the heteroatom placement impact molecular recognition. Herein, we report our discovery of benz­imid­azole and amino­phenyl­oxadiazole FPR2 agonists with low nanomolar activity.