Pharmacomodulation of torasemide led to original diuretic, neuroprotective, anticonvulsant and antithrombotic drugs

Pharmacomodulation of torasemide, a diuretic sulfonylurea, led to the discovery of two novel diuretics, a sulfonylthiourea (BM 20) and a sulfonylcyanoguanidine (BM 106). BM 27, a lipophilic sulfonylurea, exhibited neuroprotective properties associated to an anticonvulsant activity. As BM 27, two lipophilic sulfonythioureas (BM 11 and BM 34) revealed an anticonvulsant profile similar to that of phenytoin. Finally the synthesis of torasemide derivatives led to the development of a sulfonylcyanoguanidine (BM 144) with a thromboxane A2 antagonist potency.