title: Pharmacomodulation of torasemide led to original diuretic, neuroprotective, anticonvulsant and antithrombotic drugs.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, University of Liège.
authors.forename: B
authors.initials: B
authors.lastname: Masereel
authors.forename: J M
authors.initials: JM
authors.lastname: Dogné
authors.forename: J
authors.initials: J
authors.lastname: Damas
authors.forename: A
authors.initials: A
authors.lastname: Nuhrich
authors.forename: M
authors.initials: M
authors.lastname: Varache-Lembège
authors.forename: J
authors.initials: J
authors.lastname: Fontaine
authors.forename: L
authors.initials: L
authors.lastname: Pochet
authors.forename: F
authors.initials: F
authors.lastname: Somers
authors.forename: P
authors.initials: P
authors.lastname: de Tullio
authors.forename: B
authors.initials: B
authors.lastname: Pirotte
authors.forename: J
authors.initials: J
authors.lastname: Delarge
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology; D004232:Diuretics / Q000138:chemical synthesis* / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D000077786:Torsemide
chemical_list: D000927:Anticonvulsants; D004232:Diuretics; D005343:Fibrinolytic Agents; D018696:Neuroprotective Agents; D013449:Sulfonamides; D000077786:Torsemide