Reference : Synthesis and radioligand binding studies of methoxylated 1,2,3,4-tetrahydroisoquinol...
Scientific journals : Article
Human health sciences : Pharmacy, pharmacology & toxicology
Physical, chemical, mathematical & earth Sciences : Chemistry
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 [Université de Liège - ULiège > > Chimie pharmaceutique >]
Scuvée-Moreau, Jacqueline mailto [Université de Liège - ULiège > Département des sciences cognitives > Neuroscience comportementale et psychopharmacologie expér. >]
Alleva, Livia mailto [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 mailto [Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique >]
Liégeois, Jean-François mailto [ > > ]
Journal of Medicinal Chemistry
Amer Chemical Soc
Yes (verified by ORBi)
[en] Apamin ; Binding ; Amines
[fr] N-methyl-laudnosine ; N-methyl-noscapine
[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.

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