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

Abstract 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).