The aim of the present study was to examine compounds related to torasemide with respect to their ability to block the equivalent short circuit current, corresponding to the rate of chloride reabsorption, in isolated in vitro perfused cortical thick ascending limbs of Henle of the rabbit. The torasemide molecule was modified with respect to the anionic sulfonylurea group, and the secondary amine linked to the pyridine ring. Our results indicate that only few of the tested 48 torasemide-related compounds were able to inhibit from both epithelial sides like torasemide. Only few of the tested compounds were equally effective as torasemide from the lumen side. Some analogues were acting only from the luminal side and some only from the peritubular side. The correlations between structure and potency of inhibition from the luminal side allow the following conclusions: The secondary amine moiety linked to the pyridine ring (toluidine in case of torasemide) can be replaced by a cycloalkylamine or, with some loss of inhibitory potency, by alkylamines. The inhibitory potency is increased with the number of C-atoms in the cycloalkylamine substituted compounds (optimum C7 to C8) and is also depending on the length of the alkylamines (optimum C4). The secondary amine seems to be required since nitrogen cannot be replaced by -S- or -SO2-. The sulfonylurea group cannot be substituted by other anionic groups such as -SO-3 or -COO-. If the pyridine ring is replaced by a NO2-substituted phenyl ring, the inhibitory potency from the luminal side is lost. However, these compounds act still (with some loss of potency) from the peritubular side.(ABSTRACT TRUNCATED AT 250 WORDS)