Primary mono- and bis-sulfonamides obtained via regiospecific sulfochlorination of N-arylpyrazoles: inhibition profile against a panel of human carbonic anhydrases. (1st January 2017)

• Record Type: Journal Article
• Authors: Krasavin, Mikhail; Korsakov, Mikhail; Ronzhina, Oksana; Tuccinardi, Tiziano; Kalinin, Stanislav; Tanç, Muhammet; Supuran, Claudiu T.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 32:Number 1(2017)
• Page Start: 920
• Page End: 934
• Publication Date: 2017-01-01
• Subjects: Carbonic anhydrases -- isoform selectivity -- direct sulfochlorination -- mono-sulfonamides -- bis-sulfonamides -- chemoselectivity; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2017.1344236
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: A diverse set of mono- and bis-sulfonamide was obtained via a direct, chemoselective sulfochlorination of readily available yet hitherto unexplored N-arylpyrazole template. Biochemical profiling of compounds thus obtained against a panel of human carbonic anhydrases ( h CA I, h CA II, h CA IV and h CA VII) revealed a number of leads that are promising from the isoform selectivity prospective and exhibit potent inhibition profile (from nanomolar to micromolar range). The observed SAR trends have been rationalized by in silico docking of selected compounds into the active site of all four isoforms. The results reported in this paper clearly attest to the power of direct sulfochlorination as the means to create carbonic anhydrase focused sets in order to identify isoform selective inhibitors of closely related enzymes. Graphical Abstract: