Carbonic anhydrase inhibitors. Design of anticonvulsant sulfonamides incorporating indane moieties.
A series of aromatic sulfonamides incorporating indane moieties were prepared starting from commercially available 1- and 2-indanamine, and their activity as inhibitors of two carbonic anhydrase (CA, EC 4.2.1.1) isozymes, hCA I and II was studied. The new sulfonamides incorporating acetamido, 4-chloro-benzoyl, valproyl, tetra-, and pentafluorobenzoyl moieties acted as very potent inhibitors of the slow red blood cell isozyme hCA I (K(i)s in the range of 1.6-8.5 nM), which usually has a lower affinity for such inhibitors, as compared to isozyme II. Some derivatives also showed excellent hCA II inhibitory properties (K(i)s in the range of 2.3-12 nM), but the anticonvulsant activity of these sulfonamides was rather low as compared to that of other sulfonamide/sulfamate CA inhibitors, such as methazolamide. Furthermore, the 2-amino/acetamido-indane-5-sulfonic acids prepared during this work also showed interesting CA inhibitory properties, with inhibition constants in the range of 43-89 nM against the two isozymes, being among the most potent sulfonic acid CA inhibitors reported so far.
Chazalette
Celine
C
Université Joseph Fourier de Grenoble, Laboratoire d'Etudes Dynamiques et Structurales de la Sélectivité, Bât. C Chimie, 301 rue de la chimie, Domaine Universitaire, 38400 Saint-Martin d'Hères (Grenoble), France.
Masereel
Bernard
B
Rolin
Stéphanie
S
Thiry
Anne
A
Scozzafava
Andrea
A
Innocenti
Alessio
A
Supuran
Claudiu T
CT
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007189:Indans / Q000138:chemical synthesis; D051379:Mice; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology
D000927:Anticonvulsants; D002257:Carbonic Anhydrase Inhibitors; D007189:Indans; D013449:Sulfonamides; D024401:Carbonic Anhydrase I