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Bioorg Med Chem. 2017 Mar 15;25(6):1914-1925. doi: 10.1016/j.bmc.2017.02.018. Epub 2017 Feb 13.

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

Author information

1
Institutes of Chemistry and Translational Biomedicine, Saint Petersburg State University, Saint Petersburg 199034, Russian Federation. Electronic address: m.krasavin@spbu.ru.
2
The Ushinsky Yaroslavl State Pedagogical University, Yaroslavl 150000, Russian Federation.
3
Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
4
Institutes of Chemistry and Translational Biomedicine, Saint Petersburg State University, Saint Petersburg 199034, Russian Federation.
5
Neurofarba Dept., Universita degli Studi di Firenze, Florence, Italy.
6
Neurofarba Dept., Universita degli Studi di Firenze, Florence, Italy. Electronic address: claudiu.supuran@unifi.it.

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.

KEYWORDS:

Alternative binding mode; Aromatic sulfochlorination; Carbonic anhydrase inhibitors; Isoform selectivity; Primary sulfonamide; Zinc binding group

PMID:
28237553
DOI:
10.1016/j.bmc.2017.02.018
[Indexed for MEDLINE]

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