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Status | 已發表Published |
2-Arylacetamido-4-phenylamino-5-substituted pyridazinones as formyl peptide receptors agonists | |
Vergelli C.2; Schepetkin I.A.1; Ciciani G.2; Cilibrizzi A.4; Crocetti L.2; Giovannoni M.P.2; Guerrini G.2; Iacovone A.2; Kirpotina L.N.1; Khlebnikov A.I.3; Ye R.D.6; Quinn M.T.1 | |
2016-06-01 | |
Source Publication | Bioorganic and Medicinal Chemistry |
ISSN | 14643391 09680896 |
Volume | 24Issue:11Pages:2530-2543 |
Abstract | N-Formyl peptide receptors (FPRs: FPR1, FPR2, and FPR3) are G protein-coupled receptors that play key roles in modulating immune cells. FPRs represent potentially important therapeutic targets for the development of drugs that could enhance endogenous anti-inflammation systems associated with various pathologies, thereby reducing the progression of inflammatory conditions. Previously, we identified 2-arylacetamide pyridazin-3(2H)-ones as FPR1- or FPR2-selective agonists, as well as a large number of FPR1/FPR2-dual agonists and several mixed-agonists for the three FPR isoforms. Here, we report a new series of 2-arylacetamido-4-aniline pyridazin-3(2H)-ones substituted in position 5 as a further development of these FPR agonists. Chemical manipulation presented in this work resulted in mixed FPR agonists 8a, 13a and 27b, which had EC values in nanomolar range. In particular, compound 8a showed a preference for FPR1 (EC = 45 nM), while 13a and 27b showed a moderate preference for FPR2 (EC = 35 and 61 nM, respectively). Thus, these compounds may represent valuable tools for studying FPR activation and signaling. |
Keyword | Agonist Ca2++ Mobilization Formyl Peptide Receptor (Fpr) Neutrophil Pyridazin-3(2h)-one |
DOI | 10.1016/j.bmc.2016.04.019 |
URL | View the original |
Language | 英語English |
WOS ID | WOS:000374986400015 |
Scopus ID | 2-s2.0-84964684000 |
Fulltext Access | |
Citation statistics | |
Document Type | Journal article |
Collection | University of Macau |
Affiliation | 1.Montana State University - Bozeman 2.Universita degli Studi di Firenze 3.Tomskij Politehniceskij Universitet 4.Imperial College London 5.Polzunov Altai State Technical University 6.University of Macau |
Recommended Citation GB/T 7714 | Vergelli C.,Schepetkin I.A.,Ciciani G.,et al. 2-Arylacetamido-4-phenylamino-5-substituted pyridazinones as formyl peptide receptors agonists[J]. Bioorganic and Medicinal Chemistry, 2016, 24(11), 2530-2543. |
APA | Vergelli C.., Schepetkin I.A.., Ciciani G.., Cilibrizzi A.., Crocetti L.., Giovannoni M.P.., Guerrini G.., Iacovone A.., Kirpotina L.N.., Khlebnikov A.I.., Ye R.D.., & Quinn M.T. (2016). 2-Arylacetamido-4-phenylamino-5-substituted pyridazinones as formyl peptide receptors agonists. Bioorganic and Medicinal Chemistry, 24(11), 2530-2543. |
MLA | Vergelli C.,et al."2-Arylacetamido-4-phenylamino-5-substituted pyridazinones as formyl peptide receptors agonists".Bioorganic and Medicinal Chemistry 24.11(2016):2530-2543. |
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