Reference : Bis-tetrahydroisoquinoline derivatives: AG525E1, a new step in the search for non-quater...
Scientific journals : Article
Physical, chemical, mathematical & earth Sciences : Chemistry
Human health sciences : Pharmacy, pharmacology & toxicology
http://hdl.handle.net/2268/6101
Bis-tetrahydroisoquinoline derivatives: AG525E1, a new step in the search for non-quaternary non-peptidic small conductance Ca2+-activated K+ channel blockers
English
Graulich, Amaury [Université de Liège - ULg > Département de pharmacie > Chimie pharmaceutique >]
Lamy, Cédric [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Pharmacologie >]
Alleva, Livia mailto [Université de Liège - ULg > Département des sciences cognitives > Neuroscience comportementale et psychopharmacologie expér. >]
Dilly, Sébastien mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Pharmacologie >]
Chavatte, Philippe [> > > >]
Wouters, Johan [> > > >]
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 >]
2008
Bioorganic & Medicinal Chemistry Letters
18
11
3440-3445
Yes (verified by ORBi)
International
0960-894X
[en] So far, small conductance Ca2+-activated K+ channel (SK) blockers mostly consist of quaternary ammonium derivatives or peptides. Due to their physicochemical properties, these blockers are not suitable to study the physiological roles of SK channels in the central nervous system in vivo. Herein, we report the discovery of a chiral bis-tertiary amine with SK blocking properties from chemical modulation of laudanosine. AG525E1 has an affinity for SK channels (K-i = 293 nM) approximately 100-fold higher than the tertiary compound laudanosine (K-i similar to 30 mu M) and similar to the charged compound dequalinium (K-i = 221 nM). AG525E1 equipotently blocks SK1, SK2 and SK3 currents in transfected cell lines. Because of its basic and lipophilic properties, it can reach central SK targets. (c) 2008 Elsevier Ltd. All rights reserved.
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/6101
10.1016/j.bmcl.2008.03.069

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