Carbonic anhydrase inhibitors: 4-sulfamoyl-benzenecarboxamides and 4-chloro-3-sulfamoyl-benzenecarboxamides with strong topical antiglaucoma properties.

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Mincione F, Starnotti M, Menabuoni L, Scozzafava A, Casini A, Supuran CT

Carbonic anhydrase inhibitors: 4-sulfamoyl-benzenecarboxamides and 4-chloro-3-sulfamoyl-benzenecarboxamides with strong topical antiglaucoma properties.

Bioorg Med Chem Lett. 2001 Jul 9;11(13):1787-91.

PubMed ID

11425561 [ View in PubMed

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Abstract

Reaction of 4-carboxy-benzenesulfonamide or 4-chloro-3-sulfamoyl benzoic acid with carboxy-protected amino acids/dipeptides, or aromatic/heterocyclic sulfonamides/mercaptans afforded the corresponding benzene-carboxamide derivatives. These were tested as inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II and IV. Some of the new derivatives showed affinity in the low nanomolar range for isozymes CA II and IV, involved in aqueous humor secretion within the eye, and were tested as topically acting anti-glaucoma agents, in normotensive and glaucomatous rabbits. Good in vivo activity and prolonged duration of action has been observed for some of these derivatives, as compared to the clinically used drugs dorzolamide and brinzolamide. Some of the 4-chloro-3-sulfamoyl benzenecarboxamides reported here showed higher affinity for CA I than for the sulfonamide avid isozyme CA II.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Brinzolamide	Carbonic anhydrase 1	Ki (nM)	3	N/A	N/A	Details
Brinzolamide	Carbonic anhydrase 2	Ki (nM)	45	N/A	N/A	Details
Dorzolamide	Carbonic anhydrase 1	Ki (nM)	50000	N/A	N/A	Details
Dorzolamide	Carbonic anhydrase 2	Ki (nM)	9	N/A	N/A	Details