A sulphonylthiourea (BM 20) related to torasemide: a new loop diuretic with relative potassium-sparing properties.
A series of sulphonylthioureas related to torasemide, a high ceiling loop diuretic, were synthesized and found to inhibit the Na+ 2Cl- K+ co-transporter of the thick ascending limb of the loop of Henlé. Their diuretic properties were studied (30 mg kg-1) after oral administration to rats. Lipophilic derivatives, very active in-vitro, were found inactive orally and intraperitoneally in rats. The four most active compounds were examined for their dose-dependent diuresis. Three of them showed a potency, water and electrolyte excretion similar to torasemide. The fourth molecule, a sulphonylthiourea (BM 20), exhibited relative potassium-sparing properties and a minimal diuretic dose of 0.001 mg kg-1, 200 times lower than torasemide.
Masereel
B
B
Department of Medicinal Chemistry, University of Liège, Belgium.
Schynts
M
M
Krzesinski
J M
JM
Pirotte
B
B
Rorive
G
G
Delarge
J
J
D000284:Administration, Oral; D000818:Animals; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D008297:Male; D011188:Potassium / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077786:Torsemide
D004232:Diuretics; D011725:Pyridines; D013449:Sulfonamides; D013453:Sulfonylurea Compounds; C084234:BM 20; D013890:Thiourea; D011188:Potassium; D000077786:Torsemide