- Synthesis and radioligand binding studies of bis-isoquinolinium derivatives as small conductance Ca2+-activated K+ channel blockers
-
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 6,7-dimethoxy- or a 6,7,8-trimethoxy substitution. The length of the linker has no influence in the alkane derivatives. In relation to the xylene derivatives, the affinities are higher for the ortho and meta isomers. These results are well corroborated by a molecular modeling study. Finally, the most effective compounds have been tested in electrophysiological experiments on midbrain dopaminergic neurons and demonstrate the blocking potential of the apamin-sensitive after- hyperpolarization.
- Graulich, Amaury,Dilly, Sébastien,Farce, Amaury,Scuvée-Moreau, Jacqueline,Waroux, Olivier,Lamy, Cédric,Chavatte, Philippe,Seutin, Vincent,Liégeois, Jean-Fran?ois
-
-
Read Online
- BIS1,2,3,4-TETRAHYDROISOQUINOLINE DERIVATIVES AND THEIR USES AS PHARMACEUTICALS
-
Use of Bis 1,2,3,4-tetrahydroisoquinoline derivatives represented by formula (I) as SK channel blockers and for the preparation of a medicament useful for the treatment of disorders of the central nervous system.
- -
-
Page/Page column 7
(2009/04/24)
-
- Bis-tetrahydroisoquinoline derivatives: AG525E1, a new step in the search for non-quaternary non-peptidic small conductance Ca2+-activated K+ channel blockers
-
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 role
- Graulich, Amaury,Lamy, Cédric,Alleva, Livia,Dilly, Sébastien,Chavatte, Philippe,Wouters, Johan,Seutin, Vincent,Liégeois, Jean-Fran?ois
-
experimental part
p. 3440 - 3445
(2009/04/06)
-
- Synthesis and radioligand binding studies of methoxylated 1,2,3,4-tetrahydroisoquinolinium derivatives as ligands of the apamin-sensitive Ca2+-activated K+ channels
-
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 affinit
- Graulich, Amaury,Scuvée-Moreau, Jacqueline,Alleva, Livia,Lamy, Cédric,Waroux, Olivier,Seutin, Vincent,Liégeois, Jean-Fran?ois
-
p. 7208 - 7214
(2007/10/03)
-
- FUNGAL CELL WALL SYNTHESIS GENE
-
A reporter system reflecting the transport process that transports GPI-anchored proteins to the cell wall was constructed and compounds inhibiting this process were discovered. Further, genes conferring resistance to the above compounds were identified and methods of screening for compounds that inhibit the activity of the proteins encoded by these genes were developed.Therefore, through the novel compounds, the present invention showed that antifungal agents having a novel mechanism, i.e. inhibiting the process that transports GPI-anchored proteins to the cell wall, could be achieved.
- -
-
-
- Protoberberines from Reissert-Compounds VIII [1]. Oxazoloisoquinolines, New and Efficient Educts for the Synthesis of 8-Oxoprotoberberines
-
Certain benzylated oxazoloisoquinolinones readily available from Reissert compounds provided an efficient access to 8-oxoprotoberberines in three steps. A series of these new precursors as well as several oxoprotoberberines were prepared and the scope and limitation of this procedure were investigated.
- Reimann, Eberhard,Grasberger, Fritz,Polborn, Kurt
-
p. 991 - 1014
(2007/10/03)
-
- Synthesis of thalprzewalskiinone, a revision of structure
-
A direct comparison of the spectral data for synthetic 2-methyl-6,7-dimethoxy-3′-methoxy-4′-hydroxyoxobenzylisoquinoline iodide (1) and its positional isomer 2-methyl-6,7-dimethoxy-3′-hydroxy-4′-methoxyoxobenzylisoquinoline iodide (2) with the data obtain
- Al-Howiriny,Zemaitis,Gao,Hadden,Martin,Lin,Schiff Jr.
-
p. 823 - 826
(2007/10/03)
-
- IMPROVED SYNTHESIS OF DIHYDROISOQUINOLINE REISSERT COMPOUNDS
-
Conversion of a series of 3,4-dihydroisoquinolines to their corresponding Reissert compounds was improved significantly over the usual reaction conditions by buffering the reaction medium at pH 8.
- Jackson, Yvette A.,Stephenson, E. Kyle,Cava, Michael P.
-
p. 1047 - 1050
(2007/10/02)
-
- Synthesis of Dibenzoquinolizines - A New Entry to Protoberberines
-
A novel synthesis to prepare dibenzo-8-quinolizinones 8 is reported using the intramolecular cyclisation of the benzylated Reissert compounds 6 for the key step.Methylation of 8 by methyllithium gives partial deoxygenated coralynes 10 which in turn can be reduced by NaBH4 yielding the 8-methyltetrahydro-protoberberines 11.The structures are assigned by NMR-spectroscopy. Keywords.Reissert compounds; Intramolecular cyclisation; Dibenzo-8-quinolizinones; Deoxygenated coralynes; 8-Methyltetrahydro-protoberberines.
- Reimann, Eberhard,Benend, Helmut
-
p. 939 - 948
(2007/10/02)
-