Anticonvulsant sulfonamides/sulfamates/sulfamides with carbonic anhydrase inhibitory activity: drug design and mechanism of action.
The marketed antiepileptic drugs can not solve entirely the problem of seizure in patients suffering from refractory epilepsies. Therefore, new anticonvulsant compounds structurally and pharmacologically different of the currently prescribed drugs are needed. Carbonic anhydrase (CA) inhibitors are known to act as anticonvulsant since several decades while the link between CA and seizure is not straightforward. However, the recent discovery that several CA isozymes are expressed in brain and the better knowledge of their physiological/pathological role, lead to the emergence of new CA inhibitors with anticonvulsant effect including: analogues of acetazolamide, analogues of topiramate, aromatic or heterocyclic sulfonamides incorporating valproyl or adamantyl moieties. Different strategies are developed for the design of new more selective CA inhibitors with anticonvulsant properties.
Thiry
Anne
A
Drug Design and Discovery Center, FUNDP, University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium. anne.thiry@fundp.ac.be
Dogné
Jean-Michel
JM
Supuran
Claudiu T
CT
Masereel
Bernard
B
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000627:therapeutic use; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D002256:Carbonic Anhydrases / Q000378:metabolism*; D015195:Drug Design; D004827:Epilepsy / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000627:therapeutic use; D013451:Sulfonic Acids / Q000138:chemical synthesis* / Q000627:therapeutic use
D000927:Anticonvulsants; D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D013451:Sulfonic Acids; C005741:sulfamic acid; D002256:Carbonic Anhydrases