Enantiomeric Resolution with a New Chiral Stationary Phase of 7-Chloro-3-methyl-3,4-dihydro-2H1,2,4-benzothiadiazine S, S-Dioxide, a Cognition-Enhancing Benzothiadiazine Derivative

Abstract

The direct analytical and semipreparative high-performance liquid chromatographic (HPLC) resolution of the enantiomers of IDRA 21 [1, 7-chloro-3-methyl-3,-4-dihydro-2H-1,2,4-benzothiadiazine S, S-dioxide] is reported. (±)-DRA 21 administered orally to rats subjected to a water the maze cognition test elicited a performance enhancing effect. Between the two enantiomers, (+)-IDRA 21 was identified as being pharmacologically active in the water maze performance test, whereas (-)-IDRA 21 was completely devoid of activity when given in doses comparable to those of the dextrorotatory (+)-enantiomer. The design and preparation of a new chiral stationary phase (CSP) employed for the liquid chromatographic resolution of the enantiomers of racemic IDRA 21 is presented. This brush-type CSP, which has not been described before, is a “mixed” (π-donor π-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 ability to resolve the enantiomers of both π-acidic and π-basic compounds.