Substituted Pyridazin-3(2H)-ones as Highly Potent and Biased Formyl Peptide Receptor Agonists Academic Article uri icon

abstract

  • Herein we describe the development of a focused series of functionalized pyridazin-3(2 H)-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 (Cai2+) mobilization. Compound 50 showed an EC50 of 0.083 μM for phosphorylation of ERK1/2 and an approximate 20-fold bias away from Cai2+ mobilization at the hFPR1.

authors

  • Deora, Girdhar Singh
  • Qin, Cheng Xue
  • Vecchio, Elizabeth A
  • Debono, Aaron J
  • Priebbenow, Daniel L
  • Brady, Ryan M
  • Beveridge, Julia
  • Teguh, Silvia C
  • Deo, Minh
  • May, Lauren T
  • Krippner, Guy
  • Ritchie, Rebecca H
  • Baell, Jonathan B

publication date

  • 2019