Topically active carbonic anhydrase inhibitors. 1. O-acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide.
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Woltersdorf OW Jr, Schwam H, Bicking JB, Brown SL, deSolms SJ, Fishman DR, Graham SL, Gautheron PD, Hoffman JM, Larson RD, et al.
Topically active carbonic anhydrase inhibitors. 1. O-acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide.
J Med Chem. 1989 Nov;32(11):2486-92.
- PubMed ID
- 2810337 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) 6-HYDROXY-1,3-BENZOTHIAZOLE-2-SULFONAMIDE Carbonic anhydrase 2 IC 50 (nM) 4 N/A N/A Details Acetazolamide Carbonic anhydrase 2 IC 50 (nM) 10 N/A N/A Details Diclofenamide Carbonic anhydrase 2 IC 50 (nM) 40 N/A N/A Details Ethoxzolamide Carbonic anhydrase 2 IC 50 (nM) 3 N/A N/A Details