Reference : Synthesis and radioligand binding studies of bis-(8-isopropylisoquinolinium) derivatives...
Scientific journals : Article
Engineering, computing & technology : Computer science
Human health sciences : Pharmacy, pharmacology & toxicology
http://hdl.handle.net/2268/98736
Synthesis and radioligand binding studies of bis-(8-isopropylisoquinolinium) derivatives as ligands for apamin-sensitive sites on cloned SK2 and SK3 channels
English
Badarau, Eduard [Université de Liège - ULg > Département de Pharmacie-CIRM / Giga-Neurosciences > Chimie pharmaceutique / Pharmacologie > >]
Dilly, Sébastien mailto [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 mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Pharmacologie > >]
Seutin, Vincent mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Pharmacologie >]
Liégeois, Jean-François mailto [Université de Liège - ULg > Département de pharmacie > Chimie pharmaceutique >]
15-Nov-2011
Bioorganic & Medicinal Chemistry Letters
Elsevier Science
21
22
6756-6759
Yes (verified by ORBi)
International
0960-894X
1464-3405
Oxford
United Kingdom
[en] small conductance calcium-activated potassium channel ; SK ; pharmacophore ; charged nitrogens ; isoquinoline
[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.
Giga-Neurosciences / CIRM
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
SK channels
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/98736

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