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

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.