Simultaneous Determination of Enantiomerization and Hydrolysis Kinetic Parameters of Chiral N-Alkylbenzothiadiazine Derivatives

被引：11

作者：

Carrozzo, Marina M. ^{[1
]}

Cannazza, Giuseppe ^{[1
]}

Battisti, Umberto ^{[1
]}

Braghiroli, Daniela ^{[1
]}

Parenti, Carlo ^{[1
]}

机构：

[1] Univ Modena & Reggio Emilia, Dipartimento Sci Farmaceut, I-4100 Modena, Italy

来源：

CHIRALITY | 2010年 / 22卷 / 04期

关键词：

N-alkylbenzothiadiazines; stopped-flow multidimensional HPLC; dynamic HPLC; enantiomerization; hydrolysis; MULTIDIMENSIONAL GAS-CHROMATOGRAPHY; POSITIVE ALLOSTERIC MODULATORS; RATE CONSTANTS; LIQUID-CHROMATOGRAPHY; CHIROPTICAL DETECTION; 1ST-ORDER REACTIONS; UNIFIED EQUATION; ENERGY BARRIER; DYNAMIC HPLC; 1,1-DIOXIDE;

D O I：

10.1002/chir.20751

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. Chirality 22:389-397, 2010. (C) 2009 Wiley-Liss, Inc.

引用

页码：389 / 397

页数：9

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