Chazalette Celine, Masereel Bernard, Rolin Stéphanie, Thiry Anne, Scozzafava Andrea, Innocenti Alessio, Supuran Claudiu T
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.
Bioorg Med Chem Lett. 2004 Dec 6;14(23):5781-6. doi: 10.1016/j.bmcl.2004.09.061.
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.
