Enantiomers of benzothiadiazine diuretics by direct chromatographic resolution of the racemic drugs.
A number of racemic benzothiadiazine diuretics and two carbonyl analogue drugs were resolved into their optical isomers by liquid chromatography on chiral polyacrylamides 1. Enantiomeric resolution, which was, in some cases, almost complete, depended considerably on the substitution of the heterocyclic moiety of the drug molecules. Synthesis of the new adsorbent lb is described. The enantiomers of the benzothiadiazines penflutizide (2a) and bendroflumethiazide (2b) in high optical purity, as well as enriched (+)-buthiazide (2j) were obtained by repeated chromatography on a semipreparative scale. Chiroptical data, optical purity employing the chromatographic method, and first-order racemization kinetics as a function of pH in aqueous solutions were determined.
D001539:Bendroflumethiazide / Q000032:analysis; D001581:Benzothiadiazines / Q000032:analysis; D055598:Chemical Phenomena; D002621:Chemistry; D004232:Diuretics; D006852:Hydrochlorothiazide / Q000031:analogs & derivatives / Q000032:analysis; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D049993:Sodium Chloride Symporter Inhibitors / Q000032:analysis*; D013237:Stereoisomerism
D001581:Benzothiadiazines; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D001539:Bendroflumethiazide; C008781:penfluzide; C009732:buthiazide