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

Abstract

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 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 CNS. A compound, 6-tert-butyl-2-sulfamoylimidazo[2,1-b]-1,3,4-thiadiazole (8, UK-15454) 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. The compounds may be effective in treating cerebrovasular disease in the elderly.