Synthesis and radioligand binding studies of bis-isoquinolinium derivatives as small conductance Ca(2+)-activated K(+) channel blockers.

@article{Graulich2007SynthesisAR,
  title={Synthesis and radioligand binding studies of bis-isoquinolinium derivatives as small conductance Ca(2+)-activated K(+) channel blockers.},
  author={A. Graulich and S. Dilly and A. Farce and J. Scuv{\'e}e-Moreau and O. Waroux and C{\'e}dric Lamy and P. Chavatte and V. Seutin and J. Li{\'e}geois},
  journal={Journal of medicinal chemistry},
  year={2007},
  volume={50 21},
  pages={
          5070-5
        }
}
Starting from the scaffold of N-methyllaudanosine and N-methylnoscapine, which are known small conductance Ca2+-activated K+ channel blockers, original bis-isoquinolinium derivatives were synthezised and evaluated using binding studies, electrophysiology, and molecular modeling. These quaternary compounds are powerful blockers, and the most active ones have 10 times more affinity for the channels than dequalinium. The unsubstituted compounds possess a weaker affinity than the analogues having a… Expand
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