Substituted Pyridazin-3(2 H)-ones as Highly Potent and Biased Formyl Peptide Receptor Agonists.

Basic Information

ID: ALA4350966

Journal: J Med Chem

Title: Substituted Pyridazin-3(2 H)-ones as Highly Potent and Biased Formyl Peptide Receptor Agonists.

Authors: Deora GS, Qin CX, Vecchio EA, Debono AJ, Priebbenow DL, Brady RM, Beveridge J, Teguh SC, Deo M, May LT, Krippner G, Ritchie RH, Baell JB.

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 (Ca_i²⁺) mobilization. Compound 50 showed an EC₅₀ of 0.083 μM for phosphorylation of ERK1/2 and an approximate 20-fold bias away from Ca_i²⁺ mobilization at the hFPR1.

CiteXplore: 31038950

DOI: 10.1021/acs.jmedchem.8b01912

Patent ID: ┄

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