75256-57-4Relevant academic research and scientific papers
6-Methyl-2,4-disubstituted pyridazin-3(2H)-ones: A novel class of small-molecule agonists for formyl peptide receptors
Cilibrizzi, Agostino,Quinn, Mark T.,Kirpotina, Liliya N.,Schepetkin, Igor A.,Holderness, Jeff,Ye, Richard D.,Rabiet, Marie-Josephe,Biancalani, Claudio,Cesari, Nicoletta,Graziano, Alessia,Vergelli, Claudia,Pieretti, Stefano,Dal Piaz, Vittorio,Giovannoni, Maria Paola
scheme or table, p. 5044 - 5057 (2010/03/02)
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
Ismail, M. F.,El Khamry, A. A.,Shams, N. A.,El Sawy, O. M.
, p. 203 - 205 (2007/10/02)
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).
