Abstract
Recently we identified (R,S)-2-acetyl-1-(4'-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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Convulsants / chemical synthesis
-
Convulsants / chemistry
-
Convulsants / therapeutic use
-
Crystallography, X-Ray
-
Excitatory Amino Acid Antagonists / chemical synthesis*
-
Excitatory Amino Acid Antagonists / chemistry
-
Excitatory Amino Acid Antagonists / therapeutic use*
-
Male
-
Mice
-
Models, Molecular*
-
Molecular Structure
-
Rats
-
Receptors, Glutamate / metabolism*
-
Seizures / drug therapy
-
Seizures / pathology
-
Stereoisomerism
-
Tetrahydroisoquinolines / chemical synthesis*
-
Tetrahydroisoquinolines / chemistry
-
Tetrahydroisoquinolines / therapeutic use*
Substances
-
2-acetyl-1-(4'-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
-
Convulsants
-
Excitatory Amino Acid Antagonists
-
Receptors, Glutamate
-
Tetrahydroisoquinolines