Abstract
Herein we describe the development of a focused series of functionalized pyridazin-3(2H)-one-based formyl peptide receptor (FPR) agonists that demonstrate high potency and biased agonism. The compounds described demonstrated biased activation of prosurvival signaling, ERK1/2 phosphorylation, through diminution of the detrimental FPR1/2-mediated intracellular calcium (Ca i 2+ ) mobilization. Compound 50 showed an EC 50 of 0.083 μM for phosphorylation of ERK1/2 and an approximate 20-fold bias away from Ca i 2+ mobilization at the hFPR1.
Original language | English |
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Pages (from-to) | 5242-5248 |
Number of pages | 7 |
Journal | Journal of Medicinal Chemistry |
Volume | 62 |
Issue number | 10 |
DOIs | |
Publication status | Published - 23 May 2019 |