一种与托拉塞米相关的磺酰基硫脲（BM 20）：一种具有相对保钾特性的新型袢利尿剂。

A sulphonylthiourea (BM 20) related to torasemide: a new loop diuretic with relative potassium-sparing properties.

作者信息

Masereel B, Schynts M, Krzesinski J M, Pirotte B, Rorive G, Delarge J

机构信息

Department of Medicinal Chemistry, University of Liège, Belgium.

出版信息

J Pharm Pharmacol. 1993 Aug;45(8):720-4. doi: 10.1111/j.2042-7158.1993.tb07096.x.

DOI:10.1111/j.2042-7158.1993.tb07096.x

PMID:7901370

Abstract

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.

摘要

合成了一系列与高效髓袢利尿剂托拉塞米相关的磺酰硫脲类化合物，发现它们能抑制亨氏袢升支粗段的Na⁺-2Cl⁻-K⁺共转运体。给大鼠口服（30mg/kg）后研究了它们的利尿特性。在体外具有高活性的亲脂性衍生物在大鼠口服和腹腔注射时均无活性。研究了四种活性最高的化合物的剂量依赖性利尿作用。其中三种化合物的效能、水和电解质排泄与托拉塞米相似。第四个分子，一种磺酰硫脲（BM 20），具有相对的保钾特性，最小利尿剂量为0.001mg/kg，比托拉塞米低200倍。