Dihydrobenzothiadiazine 1,1-Dioxides and their Diuretic Properties

Identification of Chlorothiazide and Hydrochlorothiazide UV-A Photolytic Decomposition Products

“…4-Amino-6-iodo-1,3-benzenedisulfonamide (6)sChlorosulfonic acid (40 mL) was reacted with m-iodoaniline (8 g) by analogy to reported procedures. 1,2 The final product was recrystallized from boiling water to yield intermediate 6 (4 g, 29% yield) as a colorless solid: ESI-MS (M -H) 376 (100).…”

“…Hydrochlorothiazide (1) and chlorothiazide (1A) have proven to be clinically effective diuretics for more than 35 years since their original syntheses. 1,2 Degradation of these thiazides by hydrolysis has been well-studied. 3 Thiazides 1 and 1A have been reported to be potent photosensitizers which increase the sensitivity of skin to solar radiation.…”

Effect of the location of hydrogen abstraction on the fragmentation of diuretics in negative electrospray ionization mass spectrometry

“…Modifications of drugs such as diuretics can be caused by metabolism [2][3][4][5][6] or by intentional alterations of the molecules prior to administration in order to characterize the influence of functional groups on the efficiency of the particular remedy [7][8][9][10]. For instance, the diuretic effect of chlorothiazide (6-chloro-7-sulfamoyl-1,2,4-benzothiadiazine-1,1-dioxide) was increased by a factor of 10 by the hydration of its N-3¢C-4 double bond to hydrochlorothiazide (6-chloro-7-sulfamoyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxide) [11][12][13], and the substitution of a 2,6-dimethylanilide residue by a 2,6-dimethylpiperidyl group and a hydroxyl group by a hydrogen changes the diuretic agent xipamide to clopamide ( Figure 1). The identification of structural deviations can be accomplished by means of different ionization techniques such as electron impact ionization (EI) [14 -16] or electrospray ionization (ESI) [17][18][19], followed by MS-MS experiments with efficient collision-activated dissociation (CAD), generating structure informative fragment ions of the analytes.…”

Polarographic Reduction of 1,2,4-Benzothiadiazine-1,1-Dioxides and Related Compounds.

“…One such derivative is bendroflumethiazide, 3 -benzyl -3,4 -dihydro -6-(trifluoromethyl) -7 -sulfamyl -2H-1,3,4 -benzothiadiazine -1,1 -dioxide; the Squibb trade-mark is Naturetin. Previously, ultraviolet (2,9,10) and infrared (12,13) spectroscopy has been employed to confirm chemical structures. This study was conducted to show the relationship of reduction potential and structure of these compounds and their precursors.…”