Recently we identified (R,S)-2-acetyl-1-(40-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6) as a potent non-competitive AMPA receptor antagonist able to prevent epileptic seizures. We report here the optimized synthesis of compound 6, its resolution by chiral preparative HPLC, and the absolute configuration of (R)-enantiomer established by X-ray diffractometry. The biological tests of the single enantiomers revealed that higher anticonvulsant and antagonistic effects reside in (R)-enantiomer as also suggested by molecular modeling studies

Synthesis, resolution, stereochemistry, and molecular modeling of (R)- and (S)-2-acetyl-1-(4 '-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline AMPAR antagonists

GITTO, Rosaria;FICARRA, Rita;STANCANELLI, Rosanna;GUARDO, MARTA;DE LUCA, Laura;PAGANO, BENEDETTA;ROTONDO, Archimede;BRUNO, Giuseppe;CHIMIRRI, Alba
2007-01-01

Abstract

Recently we identified (R,S)-2-acetyl-1-(40-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6) as a potent non-competitive AMPA receptor antagonist able to prevent epileptic seizures. We report here the optimized synthesis of compound 6, its resolution by chiral preparative HPLC, and the absolute configuration of (R)-enantiomer established by X-ray diffractometry. The biological tests of the single enantiomers revealed that higher anticonvulsant and antagonistic effects reside in (R)-enantiomer as also suggested by molecular modeling studies
2007
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/1842202
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