ENANTIOMERIC RESOLUTION WITH A NEW CHIRAL STATIONARY-PHASE OF ORO-3-METHYL-3,4-DIHYDRO-2H-1,2,4-BENZOTHIADIAZINE S,S-DIOXIDE, A COGNITION-ENHANCING BENZOTHIADIAZINE DERIVATIVE

The direct analytical and semipreparative high-performance liquid chro matographic (HPLC) resolution of the enantiomers of IDRA 21 [1, oro-3- methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide] is reported. (+/-)-IDRA 21 administered orally to rats subjected to a water maze c ognition test elicited a performance enhancing effect. Between the two enantiomers, (+)-IDRA 21 was identified as being pharmacologically ac tive in the water maze performance test, whereas (-)-IDRA 21 was compl etely devoid of activity when given in doses comparable to those of th e dextrorotatory (+)-enantiomer. The design and preparation of a new c hiral stationary phase (CSP) employed for the liquid chromatographic r esolution of the enantiomers of racemic IDRA 21 is presented. This bru sh-type CSP, which has not been described before, is a ''mixed'' (pi-d onor pi-acceptor) type and is derived from (R)-N-(3,5-dinitrobenzoyl) allylglycine 2,6-dimethylanilide. It is easily prepared and possesses a relatively broad scope of applicability, as determined by its abilit y to resolve the enantiomers of both pi-acidic and pi-basic compounds.