| Literature DB >> 35707160 |
Nicholas R Wurtz1, James A Johnson1, Andrew Viet1, Pravin S Shirude2, Vishweshwaraiah Baligar2, Sudhakara Madduri2, Daniel L Cheney1, Hyunsoo Park1, John A Lupisella1, Mei-Yin Hsu1, Mojgan Abousleiman1, Michael A Galella3, Darpandeep Aulakh3, Elizabeth A Dierks1, Ricardo A Garcia1, Jacek Ostrowski1, Ellen K Kick1, Ruth R Wexler1.
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.Entities:
Year: 2022 PMID： 35707160 PMCID： PMC9190041 DOI： 10.1021/acsmedchemlett.2c00079
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.632