Simultaneous determination of enantiomerization and hydrolysis kinetic parameters of chiral N-alkylbenzothiadiazine derivatives.
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.
Carrozzo
Marina M
MM
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Modena e Reggio Emilia, Modena, Italy.
Cannazza
Giuseppe
G
Battisti
Umberto
U
Braghiroli
Daniela
D
Parenti
Carlo
C
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
D001581:Benzothiadiazines; D004364:Pharmaceutical Preparations; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D009584:Nitrogen