Topically active carbonic anhydrase inhibitors. 3. Benzofuran- and indole-2-sulfonamides

Derivatives of benzofuran- and indole-2-sulfonamide were prepared for evaluation as topically active ocular hypotensive agents. These compounds were found to be excellent inhibitors of carbonic anhydrase and to lower intraocular pressure in a rabbit model of ocular hypertension. However, the develop...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1990-02, Vol.33 (2), p.749-754
Main Authors: Graham, Samuel L, Hoffman, Jacob M, Gautheron, Pierre, Michelson, Stuart R, Scholz, Thomas H, Schwam, Harvey, Shepard, Kenneth L, Smith, Anthony M, Smith, Robert L
Format: Article
Language:English
Subjects:
Administration, Topical
Animals
benzofuran-2-sulfonamide
Benzofurans - adverse effects
Carbonic Anhydrase Inhibitors - administration & dosage
Carbonic Anhydrase Inhibitors - adverse effects
Carbonic Anhydrase Inhibitors - chemical synthesis
Chemical Phenomena
Chemistry
Chemistry, Physical
Drug Hypersensitivity
Glutathione - metabolism
Guinea Pigs
In Vitro Techniques
indole-2-sulfonamide
Indoles - adverse effects
Kinetics
Ocular Hypertension - drug therapy
Oxidation-Reduction
Rabbits
Structure-Activity Relationship
Sulfonamides
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Summary:Derivatives of benzofuran- and indole-2-sulfonamide were prepared for evaluation as topically active ocular hypotensive agents. These compounds were found to be excellent inhibitors of carbonic anhydrase and to lower intraocular pressure in a rabbit model of ocular hypertension. However, the development of these compounds for clinical use was precluded by the observation that they cause dermal sensitization in guinea pigs. A correlation between electrophilicity, as assessed by in vitro reactivity with reduced glutathione, and dermal sensitization potential was further documented.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00164a045