Document Report Card

ID: ALA1124628

Journal: J Med Chem

Title: Topically active carbonic anhydrase inhibitors. 1. O-acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide.

Authors: Woltersdorf OW, Schwam H, Bicking JB, Brown SL, deSolms SJ, Fishman DR, Graham SL, Gautheron PD, Hoffman JM, Larson RD.

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.

CiteXplore: 2810337

DOI: 10.1021/jm00131a011