Topically active carbonic anhydrase inhibitors. 1. O-Acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide

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Abstract
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.