Document Detail

SAR-studies on the importance of aromatic ring topologies in search for selective 5-HT7 receptor ligands among phenylpiperazine hydantoin derivatives.
MedLine Citation:
PMID:  24691057     Owner:  NLM     Status:  Publisher    
The current study is focused on newly developed phenylpiperazine derivatives of aromatic methylhydantoin differing in mutual positions of methyl and phenyl moieties. The new compounds were synthesized using Bucherer-Bergs reaction, two-phase alkylation, Mitsunobu reaction and/or an alkylation under microwave irradiation. The compounds developed were assessed on their affinity for serotoninergic receptors 5-HT1A, 5-HT6, 5-HT7 and α1-ARs in radioligand binding assays. Selected compounds were tested on their inhibitory effect at human 5-HT3A expressed in Xenopus Oocytes as well as on their activity at α1-adrenoceptor subtypes in functional and electrophysiological bioassays, respectively. Most of investigated compounds exhibited affinities for α1-ARs, 5-HT1A, 5-HT7 (Ki ∼ 0.8-353 nM) significantly higher than those for 5-HT6 receptors. Very weak inhibitory effect at 5-HT3A accompanied with high activity at α1D-AR subtypes were observed for selected representative compounds. Among the current series, particularly 5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-5-methylimidazolidine-2,4-dione hydrochloride (25a) displayed the highest 5-HT7 affinity with Ki = 3 nM and selectivity with 40-3600 fold towards 5-HT1A, 5-HT6, and α1-ARs.
Jadwiga Handzlik; Andrzej J Bojarski; Grzegorz Satała; Monika Kubacka; Bassem Sadek; Abrar Ashoor; Agata Siwek; Małgorzata Więcek; Katarzyna Kucwaj; Barbara Filipek; Katarzyna Kieć-Kononowicz
Related Documents :
23979747 - In vitro effects of novel ruthenium complexes in neospora caninum and toxoplasma gondii...
18843407 - Reactions of orthophthalaldehyde with ammonia and 2-aminoethanol.
21447967 - Anaphylaxis to buckwheat in an atopic child: a risk factor for severe allergy to nuts a...
23606117 - Synthesis, structure and anti-acetylcholinesterase activity of 12a-o-methyl territrem b.
16968087 - Aroma extraction dilution analysis of sauternes wines. key role of polyfunctional thiols.
24062857 - Continuous flow photocyclization of stilbenes - scalable synthesis of functionalized ph...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-3-18
Journal Detail:
Title:  European journal of medicinal chemistry     Volume:  78C     ISSN:  1768-3254     ISO Abbreviation:  Eur J Med Chem     Publication Date:  2014 Mar 
Date Detail:
Created Date:  2014-4-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0420510     Medline TA:  Eur J Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  324-339     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  The efficacy and cost-effectiveness of cell saver use in instrumented posterior correction and fusio...
Next Document:  Chromones as a privileged scaffold in drug discovery: A review.