Carbonic anhydrase inhibitors: inhibition of cytosolic isozymes I and II with sulfamide derivatives.
Article Details
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Casini A, Winum JY, Montero JL, Scozzafava A, Supuran CT
Carbonic anhydrase inhibitors: inhibition of cytosolic isozymes I and II with sulfamide derivatives.
Bioorg Med Chem Lett. 2003 Mar 10;13(5):837-40.
- PubMed ID
- 12617903 [ View in PubMed]
- Abstract
A novel class of effective CAIs has been identified, starting from a very weak carbonic anhydrase inhibitor (CAI), sulfamide, whose X-ray crystal structure in the adduct with hCA II has recently been reported. A series of N,N-disubstituted- and N-substituted-sulfamides were prepared from the corresponding amines and N-(tert-butoxycarbonyl)-N-[4-(dimethylazaniumylidene)-1,4-dihydropyridin-1-ylsulf onyl]azanide or the unstable N-(tert-butoxycarbonyl)sulfamoyl chloride. The disubstituted compounds being too bulky, were ineffective as CAIs, whereas mono-substituted derivatives (incorporating aliphatic, cyclic and aromatic moieties) as well as a bis-sulfamide, behaved as micro-nanomolar inhibitors of two cytosolic isozymes, hCA I and hCA II, responsible for critical physiological processes in higher vertebrates. Aryl-sulfamides were more effective than aliphatic derivatives. Low nanomolar inhibitors have been detected, which generally incorporated 4-substituted phenyl moieties in their molecule. This is the first example of CAIs in which low nanomolar inhibitors were generated starting from a very ineffective lead molecule.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Acetazolamide Carbonic anhydrase 1 Ki (nM) 900 N/A N/A Details Acetazolamide Carbonic anhydrase 2 Ki (nM) 12 N/A N/A Details Brinzolamide Carbonic anhydrase 1 Ki (nM) 3 N/A N/A Details Diclofenamide Carbonic anhydrase 1 Ki (nM) 1200 N/A N/A Details Diclofenamide Carbonic anhydrase 2 Ki (nM) 38 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 Ethoxzolamide Carbonic anhydrase 1 Ki (nM) 25 N/A N/A Details Ethoxzolamide Carbonic anhydrase 2 Ki (nM) 8 N/A N/A Details