Add time:08/22/2019         Source:sciencedirect.com

The pharmacology of lipophilic 4-arylamino- and 4-cycloalkylaminopyrid-3-ylsulfonyl(thio)ureas and their synthesis designed from torasemide are described. These compounds could lead to a method of inhibiting the astrocytic Na+ 2C1− K+ cotransporter and thus treating cerebral edema. Their lipophilicity and ionization constants were determined. Seven lipophilic compounds (17, 18, 22, 23, 24, 32 and 36) exhibited a high inhibitory potency (IC50 < 10 μM) and had lost the diuretic properties of torasemide. One of them, N-{[4-(cycloheptylamino)pyrid-3-yl[sulfonyl}-N′-cycloheptylurea 17 (0.1-1 mg/kg) was found to increase the gasp delay in hypoxia-exposed mice. In preliminary experiments, 17 (1–2.5 mg/kg) strongly reduced the morbidity and mortality rate of gerbils after permanent left carotid artery ligation. In vitro experiments confirmed its antiedematous activity.

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