Synthesis of benzensulfonamides linked to quinazoline scaffolds as novel carbonic anhydrase inhibitors

Carbonic anhydrase (CA) inhibitory activities of newly synthesized quinazoline-linked benzensulfonamides 10–29, 31, 32, 35, 36, and 45–51 against human CA (hCA) isoforms I, II, IX, and XII were measured and compared to that of acetazolamide (AAZ) as a standard inhibitor. Potent selective inhibitory activity against hCA I was exerted by compounds 14, 15, 17, 19, 20, 21, 24, 25, 28, 29, 31, 35, 45, 47, 49, and 51 with inhibition constant (K _I s) values of 39.4–354.7 nM that were nearly equivalent or even greater than that of AAZ (K _I , 250.0 nM). Compounds 15, 20, 24, 28, 29, 45 and 47 proved to have inhibitory activities against hCA II with (K _I s, 0.73–16.5 nM) that were similar or improved to that of AAZ (K _I , 12.0 nM). Compounds 13–29, 31–32, and 45–51 displayed potent hCA IX inhibitory activities (K _I s, 1.6–32.2 nM) that were more effective than or nearly equal to AAZ (K _I , 25.0 nM). Compounds 14, 15, 20, 21, 26, 45, and 47 exerted potent hCA XII inhibitory activities (K _I s, 5.2–9.2 nM), indicating similar CAI activities as compared to that of AAZ (K _I , 5.7 nM).