The diuretic activity of clorexolone and some related phthalimides and 1-oxoisoindolines

Abstract

Abstract N-Substituted 4-chloro-5-sulphamoylphthalimides showed diuretic activity in the rat. Reduction of the carbonyl group in the position para to the 5-sulphamoyl group in the phthalimides produced even more active compounds. The relationship between potency and the nature of the N-substituent was examined in 32 phthalimides and 10 reduced derivatives. Maximum potency was found in the N-cycloalkyl and N-cycloalkylmethyl compounds, one of which, 5-chloro-2-cyclohexyl-1-oxo-6-sulphamoylisoindoline (clorexolone), was 300 times as active as chlorothiazide in the rat. This compound was examined in more detail in both the rat and the dog.