γ-aminobutyric methyl ester-derived sulfamides as carbonic anhydrase inhibitors

Abstract

Catalytically active α‑carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes that primarily regulate the physiological concentration of proton and bicarbonate ions by means of the reversible hydration of CO2. Since such species are all essential in many biochemical processes, CAs are important molecular targets in medicinal chemistry. Here we report the microwave-assisted synthesis of new asymmetric N,N′-disubstituted sulfamides bearing the γ-aminobutyric methyl ester scaffold. The compounds were screened in vitro for their inhibition features against the human CA VII isoform (hCA VII), predominantly expressed in the Central Nervous System (CNS), and the ubiquitous isoforms hCA I and II. Overall, the sulfamides showed inhibition potencies (Ki) in the low micromolar range, with moderate selectivity towards hCA VII. These results point to this family of sulfamides as potentially useful for the treatment of CA-based CNS-related pathologies.