Article (Scientific journals)
Synthesis and radioligand binding studies of methoxylated 1,2,3,4-tetrahydroisoquinolinium derivatives as ligands of the apamin-sensitive Ca2+- activated K+ channels
Graulich, Amaury; Scuvée-Moreau, Jacqueline; Alleva, Livia et al.
2006In Journal of Medicinal Chemistry, 49 (24), p. 7208-7214
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Keywords :
Apamin; Binding; Amines; N-methyl-laudnosine; N-methyl-noscapine
Abstract :
[en] Several methoxylated 1,2,3,4-tetrahydroisoquinoliniums derived from N-methyl-laudanosine and N-methyl-noscapine were synthesized and evaluated for their affinity for apamin-sensitive binding sites. The quaternary ammonium derivatives have a higher affinity with regard to the tertiary amines. 6,7-Dimethoxy analogues possess a higher affinity than the 6,8- and 7,8- dimethoxy isomers. A 3,4-dimethoxybenzyl or a 2-naphthylmethyl moiety in C-1 position are more favorable than a 3,4-dimethoxyphenethyl group. Smaller groups such as propyl or isobutyl are unfavorable. In 6,7-dimethoxy analogues, increasing the size and lipophilicity with a naphthyl group in the C-1 position leads to a slight increase of affinity, while the same group in the 6,7,8- trimethoxy series is less favorable. The 6,7,8- trimethoxy derivative 3f is the first tertiary amine in the series to possess an affinity close to that of N-methyl-laudanosine and N-methyl-noscapine. Moreover, electrophysiological studies show that the most effective compound 4f blocks the apamin-sensitive afterhyperpolarization in rat dopaminergic neurons.
Research center :
CNCM
Disciplines :
Chemistry
Pharmacy, pharmacology & toxicology
Author, co-author :
Graulich, Amaury ;  Université de Liège - ULiège > Chimie pharmaceutique
Scuvée-Moreau, Jacqueline ;  Université de Liège - ULiège > Département des sciences cognitives > Neuroscience comportementale et psychopharmacologie expér.
Alleva, Livia ;  Université de Liège - ULiège > Pharmacologie
Lamy, Cédric ;  Université de Liège - ULiège > Pharmacologie
Waroux, Olivier ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Seutin, Vincent ;  Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Liégeois, Jean-François 
Language :
English
Title :
Synthesis and radioligand binding studies of methoxylated 1,2,3,4-tetrahydroisoquinolinium derivatives as ligands of the apamin-sensitive Ca2+- activated K+ channels
Publication date :
30 November 2006
Journal title :
Journal of Medicinal Chemistry
ISSN :
0022-2623
eISSN :
1520-4804
Publisher :
Amer Chemical Soc, Washington, United States - Washington
Volume :
49
Issue :
24
Pages :
7208-7214
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 30 January 2009

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