The Chemistry of Diuretics

Drugs Originating from the Screening of Dyes

“…They then found that when a second sulfonamido group was introduced, chloride ion excretion was markedly increased. 62 Further enhancement of activity followed on the introduction of a chlorine atom into the benzene ring. The outcome was the discovery that clofenamide was a potent carbonic anhydrase inhibitor.…”

Diuretics

“…1) evolved from the group of sulfonamide drugs known to inhibit the enzyme carbonic anhydrase. Both are derived from chlorodisulfamoyl-aniline in a condensation reaction with formic acid or formaldehyde, respectively (PETERS and ROCH-RAMEL 1969;NOVELLO and SPRAGUE 1957;SPRAGUE 1958;DESTEVENS 1963;BEYER 1958). Two of the first thiazide-type diuretics synthesized were chlorothiazide and hydrochlorothiazide.…”

Furosemide

“…These observations initiated the development of several somewhat more useful diuretics that were very potent inhibitors of this enzyme, for example, a heterocyclic sulfonamide, acetazolamide (Miller, et al, 1950), and an aromatic sulfonamide, dichlorphenamide (Sprague, 1958). Continued molecular modification in the aromatic series eventually led to the synthesis of a heterocyclic benzothiadiazine, chlorothiazide-a vastly superior orally effective sulfonamide diuretic, which Furosemide elicits a marked, equimolar excretion of Na and 0-; only trivial increase in K+ excretion; no effect on carbohydrate and uric acid metabolism_ "Taken from section II.…”