Primary mono- and bis-sulfonamides obtained via regiospecific sulfochlorination of N-arylpyrazoles: inhibition profile against a panel of human carbonic anhydrases

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 (hCA I, hCA II, hCA IV and hCA 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.

Keywords

• Carbonic anhydrases
• isoform selectivity
• direct sulfochlorination
• mono-sulfonamides
• bis-sulfonamides
• chemoselectivity