75256-52-9

Upstream product

• 5157-08-4 3-methyl-4,5-dihydro-6-oxopyridazine 
• 123-11-5 4-methoxy-benzaldehyde 

Downstream Products

• 75256-53-0 4-p-methoxyphenylmethyl-3-chloro-6-methylpyridazine 
• 75256-55-2 4-p-methoxyphenylmethyl-2,6-dimethylpyridazin-3(2H)-one 
• 86816-89-9 C₁₇H₂₀N₂O₄ 
• 1449104-95-3 4-(4-methoxybenzyl)-6-methylpyridazine-3(2H)-thione 
• 1449104-96-4 N-(4-bromophenyl)-2-[4-(4-methoxybenzyl)-6-methylpyridazin-3-ylthio]acetamide 

Relevant academic research and scientific papers

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

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 (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.

Synthesis and pharmacological evaluation of new pyridazin-based thioderivatives as formyl peptide receptor (FPR) agonists

Preclinical Research A new series of pyridazinone-based thioderivatives and pyridazine analogs was synthesized and tested for their ability to bind to the three human formyl peptide receptor (FPR) isoforms (FPR1, FPR2, and FPR3) and to activate intracellular calcium mobilization and chemotaxis in human neutrophils. Among the pyridazin-3(2H)-one derivatives tested, analogs 8b and 8c were mixed FPR1/FPR2 agonists, with median effective concentration values in the micromolar range, and were able to activate chemotaxis and Ca 2+ flux in human neutrophils in the low micromolar range. Molecular docking studies showed that interaction of a ligand with Arg205 of FPR1 is important for FPR1 agonist activity. For FPR2, differences in activity between oxygen-containing compounds and their thio-analogs were due to steric bulkiness of sulfur-containing groups.

6-Methyl-2,4-disubstituted pyridazin-3(2H)-ones: A novel class of small-molecule agonists for formyl peptide receptors

Following a ligand-based drug design approach, a potent mixed formyl peptide receptor 1 (FPR1) and formyl peptide receptor-like 1 (FPRL1) agonist (14a) and a potent and specific FPRL1 agonist (14x) were identified. These compounds belong to a large series of pyridazin-3(2H)-one derivatives substituted with a methyl group at position 6 and a methoxy benzyl at position 4. At position 2, an acetamide side chain is essential for activity. Likewise, the presence of lipophilic and/or electronegative substituents in the position para to the aryl group at the end of the chain plays a critical role for activity. Affinity forFPR1 receptors was evaluated by measuring intracellular calcium flux in HL-60 cells transfected with FPR1, FPRL1, and FPRL2. Agonists were able to activate intracellular calcium mobilization and chemotaxis in human neutrophils. Themost potent chemotactic agent (EC50 =0.6 μM) was the mixed FPR/FPRL1 agonist 14h.

Base-catalysed Condensation of Aromatic Aldehydes with 4,5-Dihydro-6-methylpyridazin-3(2H)-one

4-Arylmethyl-6-methylpyridazin-3(2H)-ones (IIIa-d) have been prepared by the condensation of aromatic aldehydes with 4,5-dihydro-6-methylpyridazin-3(2H)-one (I) in basic media.Compounds IIIa-d react in the lactim form with POCl3 to give 4-arylmethyl-3-chloro-6-methylpyridazines (Va-d), while these react in the lactam form with dimethyl sulphate to give 4-arylmethyl-2,6-dimethylpyridazin-3(2H)-ones (VIa-d).Compound IIId reacts with ethyl bromoacetate in the presence of sodium ethoxide to give the ethyl ester (VIIa) which reacts with benzylamine and hydrazine hydrate togive the corresponding N-benzylamide (VIIc) and hydrazide (VIId).The ester (VIIa) is readily hydrolysed to the corresponding acid (VIIb).