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.