6533b7dafe1ef96bd126f6a5

RESEARCH PRODUCT

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

Rita FicarraM. GuardoRosaria GittoMaria Letizia BarrecaArchimede RotondoEmilio RussoAlba ChimirriGiuseppe BrunoBenedetta PaganoGiovambattista De SarroLaura De LucaRosanna Stancanelli

subject

MaleModels MolecularMolecular modelStereochemistryClinical BiochemistryPharmaceutical ScienceConvulsantsAMPA receptorCrystallography X-RayBiochemistryChemical synthesisMicrowave-assisted synthesisEnantiomeric resolutionchemistry.chemical_compoundMiceSeizuresTetrahydroisoquinolinesTetrahydroisoquinolineDrug DiscoveryAnticonvulsantAnimalsMolecular BiologyMolecular StructureTetrahydroisoquinolineOrganic ChemistryAntagonistAbsolute configurationTetrahydroisoquinoline; Microwave-assisted synthesis; Enantiomeric resolution; AnticonvulsantBiological activityStereoisomerismRatschemistryReceptors GlutamateMolecular MedicineEnantiomerExcitatory Amino Acid Antagonists

description

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.

yearjournalcountryeditionlanguage
2007-01-22
http://hdl.handle.net/10447/5370