Abstract：
:Formyl peptide receptors (FPRs) play an essential role in the regulation of endogenous inflammation and immunity. In the present studies, a large series of pyridazin-3(2H)-one derivatives bearing an arylacetamide chain at position 2 was synthesized and tested for FPR agonist activity. The pyridazin-3(2H)-one ring was confirmed to be an appropriate scaffold to support FPR agonist activity, and its modification at the 4 and 6 positions led to the identification of additional active agonists, which induced intracellular Ca(2+) flux in HL-60 cells transfected with either FPR1, FPR2, or FPR3. Seven formyl peptide receptor 1 (FPR1)-specific and several mixed FPR1/FPR2 dual agonists were identified with low micromolar EC50 values. Furthermore, these agonists also activated human neutrophils, inducing intracellular Ca(2+) flux and chemotaxis. Finally, molecular docking studies indicated that the most potent pyridazin-3(2H)-ones overlapped in their best docking poses with fMLF and WKYMVM peptides in the FPR1 and FPR2 ligand binding sites, respectively. Thus, pyridazinone-based compounds represent potential lead compounds for further development of selective and/or potent FPR agonists.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Giovannoni MP,Schepetkin IA,Cilibrizzi A,Crocetti L,Khlebnikov AI,Dahlgren C,Graziano A,Dal Piaz V,Kirpotina LN,Zerbinati S,Vergelli C,Quinn MTdoi
10.1016/j.ejmech.2013.03.066subject
Has Abstractpub_date
2013-06-01 00:00:00pages
512-28eissn
0223-5234issn
1768-3254pii
S0223-5234(13)00226-2journal_volume
64pub_type
杂志文章abstract：:With the aim of discovering potent and selective kinase inhibitors targeting ROS1 kinase, we designed, synthesized and screened a series of new pyrazol-4-ylpyrimidine derivatives based on our previously discovered lead compound KIST301072. Compounds 6a-e and 7a-e showed good to excellent activities against ROS1 kinase...
journal_title：European journal of medicinal chemistry
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abstract：:In the present paper, a fast and automated method for the synthesis of (13)N-labelled azo compounds is reported for the first time. The labelling strategy is based on trapping [(13)N]NO(2)(-) in an anion exchange resin. The reaction with primary aromatic amines in acidic media led to the formation of the corresponding...
journal_title：European journal of medicinal chemistry
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abstract：:Five series of thiourea derivatives bearing benzothiazole moiety (20 compounds) were efficiently synthesized and evaluated for antimicrobial and anticancer activities. The results indicated that the compounds possessed a broad spectrum of activity against the tested microorganisms and showed higher activity against fu...
journal_title：European journal of medicinal chemistry
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abstract：:Phenolic acids are ubiquitous antioxidants accounting for approximately one third of the phenolic compounds in our diet. Their importance was supported by epidemiological studies that suggest an inverse relationship between dietary intake of phenolic antioxidants and the occurrence of diseases, such as cancer and neur...
journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
pub_type： 杂志文章,评审
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abstract：:A new series of indolo[1,2-c]quinazoline derivatives were prepared in good yield through reaction of 2-(o-aminophenyl)indole with a variety of arylaldehydes. The structures of the newly synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR and mass spectral studies and elemental analysis. All the title compo...
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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abstract：:The ruthenium DMSO complexes cis-Ru(II)C12(DMSO)4 and [(DMSO)2H][trans-Ru(III)Cl4(DMSO)2] reacted with 4-(3'-chloro-4'-fluoroanilino)-6-(2-(2-aminoethyl)aminoethoxy)-7-methoxyquinazoline (L1), 4-(3'-chloro-4'-fluoroanilino)-6-(2-(1H-imidazol-1-yl)ethoxy)-7-methoxy quinazoline (L2), N-(benzo[d]imidazol-4-yl)-6,7-dimeth...
journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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abstract：:Chalcogen-containing β-lapachone derivatives were synthesized using a straightforward methodology and evaluated against several cancer cell lines (leukaemia, human colon carcinoma, prostate, human metastatic prostate, ovarian, central nervous system and breast), showing, in some cases, IC50 values below 1 μM. The cyto...
journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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doi：10.1016/j.ejmech.2008.10.030
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abstract：:With an aim of developing novel protein tyrosine phosphatase (PTP) 1B inhibitors based on sugar scaffolds, a focused library of benzyl 6-triazolo(hydroxy)benzoic glucosides was efficiently constructed via the modular and selective Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddtion (click chemistry). These glycoconj...
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abstract：:STAT3 is an attractive therapeutic target for cancer therapy. However, due to low potency or poor druggability, none of its inhibitors are clinically available. Herein, a series of aminobenzo[b]thiophene 1, 1-dioxides with good drug-likeness properties were designed, synthesized and evaluated as STAT3 inhibitors. Most...
journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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abstract：:We previously described a series of imidazole-based inhibitors substituted at N-1 with an arylethanone chain as interesting inhibitors of neuronal nitric oxide synthase (nNOS), endowed with good selectivity vs endothelial nitric oxide synthase (eNOS). As a follow up of these studies, several analogs characterized by t...
journal_title：European journal of medicinal chemistry
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doi：10.1016/j.ejmech.2012.01.002
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abstract：:A new series of anthracene-9, 10-dione derivatives have been synthesized to increase cytotoxic activity against human papillomavirus (HPV) positive cancer cell line, CaSki. The highest cytotoxicity was achieved by 4-(benzylamino)-9,10-dioxo-4a,9,9a,10-tetrahydroanthracen-1-yl 4-ethylbenzenesulfonate (5) with the inhib...
journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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abstract：:Malaria, one of the most severe global diseases, infects nearly 300 million people causing death of about a million population annually. Herein we have reported design, synthesis and biological evaluation of potent antimalarial compounds that target melatonin hormone as a potential pathway for the inhibition of the pa...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2019.02.019
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abstract：:Cancer, an uncontrolled and rapid proliferation of abnormal cells, has become one of the leading cause of death worldwide. The development of resistance among the numerous drugs in clinical use has provided strong impetus for the identification and development of novel cancer therapeutics. β-carbolines constitute an i...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章,评审
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abstract：:The cure rate of pediatric acute lymphoblastic leukemia (ALL) has significantly improved in the past thirty years, however not all patient cohorts respond well to current chemotherapy regimens. Among the high risk patient cohort is infants with MLL-rearranged (MLL-r) B-ALL, which remains dismal with an overall surviva...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2016.02.034
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abstract：:A wide variety of small molecules with diverse molecular scaffolds inhibit microtubule formation. In this article we report a one-pot procedure for the preparation of a novel 2-(N-pyrrolidinyl)-4-amino-5-(3',4',5'-trimethoxybenzoyl)thiazole in which the size of the substituent at the C-2 position of the thiazole ring ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2011.10.013
更新日期：2011-12-01 00:00:00
