Carbonic anhydrase inhibitors. Inhibition of isoforms I, II, IV, VA, VII, IX, and XIV with sulfonamides incorporating fructopyranose–thioureido tails

Bioorganic & Medicinal Chemistry Letters
2007.0

Abstract

A series of aromatic/heterocyclic sulfonamides incorporating 2,3:4,5-bis-O-(isopropylidene)-beta-d-fructopyranosyl-thioureido moieties has been synthesized and assayed for the inhibition of seven human isoforms of the zinc enzyme carbonic anhydrase (hCA, EC 4.2.1.1). The new derivatives behaved as weak hCA I inhibitors (K(I)s of 9.4 -13.3microM), were efficient hCA II inhibitors (K(I)s of 6-750nM), and slightly inhibited isoforms hCA IV and hCA VA. Only the sulfanilamide derivative showed efficient and selective inhibition of hCA IV (K(I) of 10nM). These derivatives also showed excellent hCA VII inhibitory activity (K(I)s of 10-79nM), being less efficient as inhibitors of the transmembrane isoforms hCA IX (K(I)s of 10-4500nM) and hCA XIV (K(I)s of 21-3500nM). Two of the new compounds showed anticonvulsant action in a maximal electroshock seizure test in mice, with the fluorosulfanilamide derivative being a more efficient anticonvulsant than the antiepileptic drug topiramate.

DOI： 10.1016/j.bmcl.2007.03.008

Knowledge Graph

Similar Paper

Carbonic anhydrase inhibitors. Inhibition of isoforms I, II, IV, VA, VII, IX, and XIV with sulfonamides incorporating fructopyranose–thioureido tails
Bioorganic & Medicinal Chemistry Letters 2007.0
Carbonic anhydrase inhibitors. Inhibition of the human cytosolic isozyme VII with aromatic and heterocyclic sulfonamides
Bioorganic & Medicinal Chemistry Letters 2005.0
Carbonic anhydrase inhibitors: Inhibition of the transmembrane isozyme XIV with sulfonamides
Bioorganic & Medicinal Chemistry Letters 2005.0
Carbonic anhydrase inhibitors. Phenacetyl-, pyridylacetyl- and thienylacetyl-substituted aromatic sulfonamides act as potent and selective isoform VII inhibitors
Bioorganic & Medicinal Chemistry Letters 2009.0
Anticonvulsant 4-Aminobenzenesulfonamide Derivatives with Branched-Alkylamide Moieties: X-ray Crystallography and Inhibition Studies of Human Carbonic Anhydrase Isoforms I, II, VII, and XIV
Journal of Medicinal Chemistry 2011.0
Carbonic anhydrase inhibitors: Synthesis and inhibition of the human carbonic anhydrase isoforms I, II, VII, IX and XII with benzene sulfonamides incorporating 4,5,6,7-tetrabromophthalimide moiety
Bioorganic & Medicinal Chemistry 2013.0
Discovery of Benzenesulfonamide Derivatives as Carbonic Anhydrase Inhibitors with Effective Anticonvulsant Action: Design, Synthesis, and Pharmacological Evaluation
Journal of Medicinal Chemistry 2018.0
Carbonic anhydrase inhibitors. Inhibition of cytosolic isoforms I and II, and extracellular isoforms IV, IX, and XII with sulfamides incorporating sugar moieties
Bioorganic & Medicinal Chemistry Letters 2007.0
Carbonic anhydrase inhibitors. Synthesis, molecular structures, and inhibition of the human cytosolic isozymes I and II and transmembrane isozymes IX, XII (cancer-associated) and XIV with novel 3-pyridinesulfonamide derivatives
European Journal of Medicinal Chemistry 2011.0
Discovery of Benzenesulfonamides with Potent Human Carbonic Anhydrase Inhibitory and Effective Anticonvulsant Action: Design, Synthesis, and Pharmacological Assessment
Journal of Medicinal Chemistry 2017.0