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

Article Details

Citation

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
DrugTargetPropertyMeasurementpHTemperature (°C)
6-HYDROXY-1,3-BENZOTHIAZOLE-2-SULFONAMIDECarbonic anhydrase 2IC 50 (nM)4N/AN/ADetails
AcetazolamideCarbonic anhydrase 2IC 50 (nM)10N/AN/ADetails
DiclofenamideCarbonic anhydrase 2IC 50 (nM)40N/AN/ADetails
EthoxzolamideCarbonic anhydrase 2IC 50 (nM)3N/AN/ADetails