Human carbonic anhydrase inhibitory profile of mono- and bis-sulfonamides synthesized via a direct sulfochlorination of 3- and 4-(hetero)arylisoxazol-5-amine scaffolds. Issue 6 (15th March 2017)

• Record Type: Journal Article
• Authors: Krasavin, Mikhail; Korsakov, Mikhail; Zvonaryova, Zhanna; Semyonychev, Evgenii; Tuccinardi, Tiziano; Kalinin, Stanislav; Tanç, Muhammet; Supuran, Claudiu T.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 6(2017)
• Page Start: 1914
• Page End: 1925
• Publication Date: 2017-03-15
• Subjects: Carbonic anhydrase inhibitors -- Isoform selectivity -- Zinc binding group -- Primary sulfonamide -- Aromatic sulfochlorination -- Alternative binding mode; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.02.018
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Three distinct series of isoxazole-based primary mono- and bis-sulfonamides have been synthesized via direct sulfochlorination, each of them delivering nanomolar inhibitors of human carbonic anhydrase. Certain pronounced SAR trends have been established and rationalized by in silico docking. These findings expand the structure-activity knowledge base for heterocycle-containing sulfonamide carbonic anhydrase inhibitors and further validate the power of direct electrophilic sulfochlorination as a means of introducing the pharmacophoric primary sulfonamide group into structurally diverse aromatic precursors.