Carbonic anhydrase inhibitors: the first on-resin screening of a 4-sulfamoylphenylthiourea library.

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Innocenti A, Casini A, Alcaro MC, Papini AM, Scozzafava A, Supuran CT

Carbonic anhydrase inhibitors: the first on-resin screening of a 4-sulfamoylphenylthiourea library.

J Med Chem. 2004 Oct 7;47(21):5224-9.

PubMed ID
15456265 [ View in PubMed
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Abstract

Sulfonamide carbonic anhydrase (CA) inhibitors are widely employed in the diagnosis and treatment of diverse diseases such as glaucoma and different neuromuscular disorders. Moreover, an emerging area is represented by their use in the prevention and treatment of tumors. In this paper we propose an optimized synthesis of on-resin CA inhibitor libraries to be used for a high-throughput biological screening. A library of 4-sulfamoylphenylthioureas, previously described to be attractive candidates as novel antiglaucoma drugs, has been synthesized by a solid-phase approach, avoiding the formation of thiohydantoin side products. The on-resin screening assay has been developed for the inhibition tests of different CA isozymes with the on-resin supported sulfonamides, allowing the direct identification of the biologically active lead compounds. These results allow the development of new designed libraries in the solid phase of sulfonamide CA inhibitors characterized by a set of prefixed parameters to be used as possible drug candidates.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AcetazolamideCarbonic anhydrase 1Ki (nM)900N/AN/ADetails
AcetazolamideCarbonic anhydrase 2Ki (nM)12N/AN/ADetails
DiclofenamideCarbonic anhydrase 1Ki (nM)1200N/AN/ADetails
DiclofenamideCarbonic anhydrase 2Ki (nM)38N/AN/ADetails
DorzolamideCarbonic anhydrase 1Ki (nM)50000N/AN/ADetails
DorzolamideCarbonic anhydrase 2Ki (nM)9N/AN/ADetails
EthoxzolamideCarbonic anhydrase 1Ki (nM)25N/AN/ADetails
EthoxzolamideCarbonic anhydrase 2Ki (nM)8N/AN/ADetails