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

S L Graham; J M Hoffman; P Gautheron; S R Michelson; T H Scholz; H Schwam; K L Shepard; A M Smith; R L Smith; J M Sondey

doi:10.1021/jm00164a045

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

J Med Chem. 1990 Feb;33(2):749-54. doi: 10.1021/jm00164a045.

Authors

S L Graham¹, J M Hoffman, P Gautheron, S R Michelson, T H Scholz, H Schwam, K L Shepard, A M Smith, R L Smith, J M Sondey, et al.

Affiliation

¹ Department of Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486.

PMID: 2299640
DOI: 10.1021/jm00164a045

Abstract

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.

MeSH terms

Administration, Topical
Animals
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
Indoles / adverse effects
Kinetics
Ocular Hypertension / drug therapy
Oxidation-Reduction
Rabbits
Structure-Activity Relationship
Sulfonamides

Substances

Benzofurans
Carbonic Anhydrase Inhibitors
Indoles
Sulfonamides
Glutathione