Enantiomeric resolution with a new chiral stationary phase of 7-chloro-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 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. (+/-)-IDRA 21 administered orally to rats subjected to a water 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" (pi-donor 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 ability to resolve the enantiomers of both pi-acidic and pi-basic compounds.
D000818:Animals; D001581:Benzothiadiazines / Q000737:chemistry* / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018697:Nootropic Agents / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D001581:Benzothiadiazines; D018697:Nootropic Agents; C091420:IDRA 21