New isomeric classes of topically active ocular hypotensive carbonic anhydrase inhibitors: 5-Substituted thieno[2,3-b]thiophene-2-sulfonamides and 5-substituted theio[3,2-b]thiophene-2-sulfonamides

Article abstract of DOI:10.1021/jm00110a008

A series of 5-substituted thieno[2,3-b]- and thieno[3,2-b]thiophene-2-sulfonamides was prepared and evaluated for topical ocular hypotensive activity in glaucoma models. The 5-substituents were varied to maximize both inhibitory potency against carbonic anhydrase and water solubility. At the same time, these substituents were varied in order to obtain compounds with the appropriate pK(a) to minimize pigment binding in the iris. All of these variables were optimized in the best compound, 5-[[(methoxyethyl)](methoxyethyl)ethyl]amino]methyl]thieno[2,3-b] thiophene-2-sulfonamide hydrochloride (55).