Topically Active Carbonic Anhydrase Inhibitors. 1. O-Acyl Derivatives of 6-Hydroxybenzothiazole-2-sulfonamide

Article abstract of DOI:10.1021/jm00131a011

A series of O-acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide (4, L-643,799) was prepared and the potential utility of each series member as a topically active inhibitor of ocular carbonic anhydrase was determined.In vitro studies showed these esters to be substrates for ocular esterases which liberate 4 during corneal translocation.The most interesting series member, 2-sulfamoyl-6-benzothiazolyl 2,2-dimethylpropionate (22, L-645,151), acting as a prodrug form of 4, was found to enhance delivery through the isolated albino rabbit cornea by 40-fold when compared to the parent phenol 4.Studies in rabbits revealed that 22 is a potent topically active ocular hypotensive carbonic anhydrase inhibitor.