UM
6-Methyl-2,4-disubstituted pyridazin-3(2H)-ones: A novel class of small-molecule agonists for formyl peptide receptors
Cilibrizzi A.2; Quinn M.T.1; Kirpotina L.N.1; Schepetkin I.A.1; Holderness J.1; Ye R.D.3; Rabiet M.-J.4; Biancalani C.2; Cesari N.2; Graziano A.2; Vergelli C.2; Pieretti S.; Dal Piaz V.2; Giovannoni M.P.2
2009-08-27
Source PublicationJournal of Medicinal Chemistry
ISSN00222623
Volume52Issue:16Pages:5044-5057
AbstractFollowing 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 (EC =0.6 μM) was the mixed FPR/FPRL1 agonist 14h. © 2009 American Chemical Society.
DOI10.1021/jm900592h
URLView the original
Language英語
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Cited Times [WOS]:32   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Montana State University - Bozeman
2.Universita degli Studi di Firenze
3.University of Illinois at Chicago
4.CEA Grenoble
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Cilibrizzi A.,Quinn M.T.,Kirpotina L.N.,et al. 6-Methyl-2,4-disubstituted pyridazin-3(2H)-ones: A novel class of small-molecule agonists for formyl peptide receptors[J]. Journal of Medicinal Chemistry,2009,52(16):5044-5057.
APA Cilibrizzi A..,Quinn M.T..,Kirpotina L.N..,Schepetkin I.A..,Holderness J..,...&Giovannoni M.P..(2009).6-Methyl-2,4-disubstituted pyridazin-3(2H)-ones: A novel class of small-molecule agonists for formyl peptide receptors.Journal of Medicinal Chemistry,52(16),5044-5057.
MLA Cilibrizzi A.,et al."6-Methyl-2,4-disubstituted pyridazin-3(2H)-ones: A novel class of small-molecule agonists for formyl peptide receptors".Journal of Medicinal Chemistry 52.16(2009):5044-5057.
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