Cerebrovasodilatation through selective inhibition of the enzyme carbonic anhydrase. 2. Imidazo[2,1-b]thiadiazole and imidazo[2,1-b]thiazolesulfonamides

• Published in: Journal of medicinal chemistry Vol. 23; no. 2; pp. 117 - 121
• Main Authors: Barnish, Ian T, Cross, Peter E, Dickinson, Roger P, Gadsby, Brian, Parry, Michael J, Randall, Michael J, Sinclair, Ian W
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.02.1980
• Subjects: Animals; Anticonvulsants - chemical synthesis; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - pharmacology; Cerebrovascular Circulation - drug effects; Diuretics - chemical synthesis; Dogs; In Vitro Techniques; Male; Mice; Rats; Structure-Activity Relationship; Sulfonamides - chemical synthesis; Sulfonamides - pharmacology; Thiadiazoles - chemical synthesis; Thiadiazoles - pharmacology; Thiazoles - chemical synthesis; Thiazoles - pharmacology
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00176a003

A series of imidazo[2,1-b]thiadiazole and imidazo[2,1-b]thiazolesulfonamide carbonic anhydrase inhibitors is described and their anticonvulsant activities are listed. Many of the compounds have the same degree of ionization as acetazolamide and methazolamide, but their higher lipophilicity means that they are more able to penetrate into the central nervous system. One compound, 6-tert-butyl-2-sulfamoylimidazo[2,1-b]-1,3,4-thiadiazole (8, UK-15,454) had an anticonvulsant ED50 of 2.6 mg/kg when administered orally to mice. 8 selectively increased cerebral blood flow in animals without producing a high level of metabolic acidosis.