Discovery of Heteroaryl Urea Isosteres for Formyl Peptide Receptor 2 Agonists.

Authors :: Wurtz NR
Johnson JA
Viet A
Shirude PS
Baligar V
Madduri S
Cheney DL
Park H
Lupisella JA
Hsu MY
Abousleiman M
Galella MA
Aulakh D
Dierks EA
Garcia RA
Ostrowski J
Kick EK
Wexler RR
Source :: ACS medicinal chemistry letters [ACS Med Chem Lett] 2022 May 25; Vol. 13 (6), pp. 943-948. Date of Electronic Publication: 2022 May 25 (Print Publication: 2022).
Publication Year :: 2022
Abstract: 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.<br />Competing Interests: The authors declare no competing financial interest.<br /> (© 2022 American Chemical Society.)