One-Pot Procedure for the Synthesis of Asymmetric Substituted Ureido Benzene Sulfonamides as Effective Inhibitors of Carbonic Anhydrase Enzymes

Vannozzi, G.; Vullo, D.; Angeli, A.; Ferraroni, M.; Combs, J.; Lomelino, C.; Andring, J.; Mckenna, R.; Bartolucci, G.; Pallecchi, M.; Lucarini, L.; Sgambellone, S.; Masini, E.; Carta, F.; Supuran, C. T.

doi:10.1021/acs.jmedchem.1c01906

We report a one-pot procedure for the synthesis of asymmetrical ureido-containing benzenesulfonamides based on in situ generation of the corresponding isocyanatobenezenesulfonamide species, which were trapped with the appropriate amines. A library of new compounds was generated and evaluated in vitro for their inhibition properties against a representative panel of the human (h) metalloenzymes carbonic anhydrases (EC 4.2.1.1), and the best performing compounds on the isozyme II (i.e., 7c, 9c, 11g, and 12c) were screened for their ability to reduce the intraocular pressure in glaucomatous rabbits. In addition, the binding modes of 7c, 11f, and 11g were assessed by means of X-ray crystallography.

One-Pot Procedure for the Synthesis of Asymmetric Substituted Ureido Benzene Sulfonamides as Effective Inhibitors of Carbonic Anhydrase Enzymes / Vannozzi G.; Vullo D.; Angeli A.; Ferraroni M.; Combs J.; Lomelino C.; Andring J.; Mckenna R.; Bartolucci G.; Pallecchi M.; Lucarini L.; Sgambellone S.; Masini E.; Carta F.; Supuran C.T.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - ELETTRONICO. - 65:(2021), pp. 824-837. [10.1021/acs.jmedchem.1c01906]