Design and synthesis of novel 1,3-diaryltriazene-substituted sulfonamides as potent and selective carbonic anhydrase II inhibitors

Abstract

A series of novel 1,3-diaryltriazene-substituted sulfonamides was synthesized by reaction of diazonium salt of 4-amino benzenesulfonamide with substituted aromatic amines. The obtained 1,3-diaryltriazene-substituted sulfonamides were investigated as inhibitors of four selected human carbonic anhydrase (CA, EC 4.2.1.1) isoforms (hCA I, hCA II, hCA VII and hCA IX) are involved in various diseases such as glaucoma, epilepsy, retinitis pigmentosa, cancer, obesity, etc. All these sulfonamides were found to be potent inhibitors of the cytosolic isoform hCA II with low nanomolar to sub-nanomolar K(i)s in the range of 0.2-21.5 nM, as well as a moderate selectivity against other cytosolic isoforms hCA I and hCA VII, and great selectivity against membrane-bound isoform hCA IX was observed. Since hCA II is an important drug target for antiglaucoma agents and diuretics, these isoform-selective inhibitors may be considered of interest as tools for the development of new candidates for these conditions. (C) 2018 Elsevier Inc. All rights reserved.