4-(3-Alkyl/Benzyl-Guanidino)Benzenesulfonamides as Selective Carbonic Anhydrase VII Inhibitors

Journal of Enzyme Inhibition and Medicinal Chemistry 2022
Morteza Abdoli, Simone Giovannuzzi, C.T Supuran, Raivis Žalubovskis

The treatment of chronic neuropathic pain remains one of the most challenging of all neurological diseases and very much an art. There exists no consensus for the optimal management of this condition at the moment. Gaining inspiration from recent studies which pointed out the involvement of brain-associated carbonic anhydrase (CA, EC 4.2.1.1) isoform VII in the pathology of various neurodegenerative diseases, which highlighted the relationship between selective inhibition of this isozyme and relieve of neuropathic pain, herein we report the synthesis and CA VII inhibitory activity of novel 4-(3-alkyl/benzyl-guanidino)benzenesulfonamides. Ten benzyl-substituted and five alkyl-substituted 4-guanidinobenzenesulfonamide derivatives were obtained, some of which (7c, 7h, 7m and 7o) exhibited satisfactory selectivity towards CA VII over CA I and II, with KI-s in the subnanomolar range and good selectivity indexes for inhibiting the target versus the off-target isoforms.

Keywords
Neurological diseases, neuropathic pain, carbonic anhydrase isozyme VII, sulfonamides, guanidine-benzenesulfonamides
DOI
10.1080/14756366.2022.2080816
Hyperlink
https://www.tandfonline.com/doi/full/10.1080/14756366.2022.2080816

Abdoli, M., Giovannuzzi, S., Supuran, C., Žalubovskis, R. 4-(3-Alkyl/Benzyl-Guanidino)Benzenesulfonamides as Selective Carbonic Anhydrase VII Inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, 2022, Vol. 37, No. 1, pp.1568-1576. ISSN 1475-6366. e-ISSN 1475-6374. Available from: doi:10.1080/14756366.2022.2080816

Publication language
English (en)