title: Simultaneous determination of enantiomerization and hydrolysis kinetic parameters of chiral N-alkylbenzothiadiazine derivatives.
abstract: On-column stopped flow multidimensional HPLC (sfMDHPLC) and dynamic high-performance liquid chromatography were applied to investigate the influence of alkyl substituents at the sulfonamidic and amino moieties of benzothiadiazine 1,1-dioxide derivatives on hydrolysis and enantiomerization rate constants. The data obtained indicate the presence of pyrrolo substituent at the 3,4 positions on benzothiadiazine rings inhibits the hydrolysis, whereas the enantiomerization occurs in acidic medium. Hydrolysis rates are quite similar for the two benzothiadiazines methyl substituted to nitrogen at 2- and 4-positions. Conversely, enantiomerization rate of 4-N-methyl substituted is significantly higher than 2-N-methyl substituted.
authors: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Modena e Reggio Emilia, Modena, Italy.
authors: Marina M
authors: MM
authors: Carrozzo
authors: Giuseppe
authors: G
authors: Cannazza
authors: Umberto
authors: U
authors: Battisti
authors: Daniela
authors: D
authors: Braghiroli
authors: Carlo
authors: C
authors: Parenti
mesh_terms: D001581:Benzothiadiazines / Q000737:chemistry* / Q000302:isolation & purification; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002845:Chromatography / Q000295:instrumentation / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008956:Models, Chemical; D009584:Nitrogen / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000302:isolation & purification; D013237:Stereoisomerism; D013816:Thermodynamics; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000737:chemistry
chemical_list: D001581:Benzothiadiazines; D004364:Pharmaceutical Preparations; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D009584:Nitrogen