ORBi: Badarau Eduard - Synthesis and radioligand binding studies of bis-(8-isopropylisoquinolinium) derivatives as ligands for apamin-sensitive sites on cloned SK2 and SK3 channels

Reference : Synthesis and radioligand binding studies of bis-(8-isopropylisoquinolinium) derivatives...


	Document type :	Scientific journals : Article
	Discipline(s) :	Human health sciences : Pharmacy, pharmacology & toxicology Engineering, computing & technology : Computer science
	To cite this reference:	http://hdl.handle.net/2268/98736

Title :	Synthesis and radioligand binding studies of bis-(8-isopropylisoquinolinium) derivatives as ligands for apamin-sensitive sites on cloned SK2 and SK3 channels
Language :	English
Author, co-author :	Badarau, Eduard [Université de Liège - ULg > Département de Pharmacie-CIRM / Giga-Neurosciences > Chimie pharmaceutique / Pharmacologie > >]
	Dilly, Sébastien [Université de Liège - ULg > Département de Pharmacie-CIRM / Giga-Neurosciences > Chimie pharmaceutique / Pharmacologie > >]
	Dufour, Fabien [Université de Liège - ULg > Département de Pharmacie-CIRM / Giga-Neurosciences > Chimie pharmaceutique / Pharmacologie > >]
	Poncin, Sylvie [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Pharmacologie > >]
	Seutin, Vincent [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Pharmacologie >]
	Liégeois, Jean-François [Université de Liège - ULg > Département de pharmacie > Chimie pharmaceutique >]
Publication date :	15-Nov-2011
Journal title :	Bioorganic & Medicinal Chemistry Letters
Publisher :	Elsevier Science
Volume :	21
Issue/season :	22
Pages :	6756-6759
Audience :	International
ISSN :	0960-894X
e-ISSN :	1464-3405
City :	Oxford
Country :	United Kingdom
Keywords :	[en] small conductance calcium-activated potassium channel ; SK ; pharmacophore ; charged nitrogens ; isoquinoline
Abstract :	[en] A structure-activity relationship study of N-methyl-laudanosine, a SK channel blocker, has indicated that the 6,7-dimethoxy group could be successfully replaced by a hydrophobic moiety such as an isopropyl substituent in position 8 of the isoquinoline ring. In the present study, bis-(8-isopropyl-isoquinolinium) derivatives (2a-e) were synthesized and tested for their affinity for cloned SK2 and SK3 channels in comparison with their 6,7-dimethoxy analogues (4a-f). Several ligands were investigated, both in flexible (propyl, butyl and pentyl) and rigid (m- or p-xylyl) series, the m-xylyl derivative (2d) having the best profile in terms of affinity and selectivity for SK3/SK2 channels. Molecular studies showed that the optimal conformation of compound 2d fits well with our SK pharmacophore model.
Research units :	Giga-Neurosciences / CIRM
Funders :	Fonds de la Recherche Scientifique-FNRS (F.R.S.-FNRS) ; Fonds Spéciaux pour la Recherche of the University of Liège (Belgium) ; SPW DGO6 PPP NEUREDGE convention 816859
Name of the research project :	SK channels
Target :	Researchers ; Professionals ; Students
Permalink :	http://hdl.handle.net/2268/98736

File(s) associated to this reference

Fulltext file(s):

	File	Commentary	Version	Size	Access
Restricted access	SK-isopropylBMCLrevised130908.pdf		Author preprint	418.06 kB	Request copy

All documents in ORBi are protected by a user license.

Dspace v1.5