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Bioorg Med Chem. 2013 Mar 15;21(6):1555-63. doi: 10.1016/j.bmc.2012.05.037. Epub 2012 May 26.

Superacid synthesis of halogen containing N-substituted-4-aminobenzene sulfonamides: new selective tumor-associated carbonic anhydrase inhibitors.

Author information

1
Superacid group in « Glycochimie, Superacide et Chimie des systèmes » team-Université de Poitiers, CNRS UMR 7285 IC2MP, 4, avenue Michel Brunet, F-86022 Poitiers Cedex, France.

Abstract

A series of new, halogen containing N-substituted 4-aminobenzenesulfonamides were synthesized by using superacid HF/SbF5 chemistry and investigated as inhibitors of several human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, that is, the cytosolic hCA I and II and, the tumor-associated transmembrane isoforms hCA IX and XII. Despite the substitution of the sulfonamide function, the presence of fluorine atom(s) in β position of the sulfonamide function strongly favors hCA inhibition. A similar effect of the β-fluorinated alkyl substitution on the amino function has been also observed. Among the tested compounds, several chlorinated derivatives have been identified as selective nanomolar, tumor-associated isoforms inhibitors. These non-primary sulfonamides probably bind in the coumarin-binding site, at the entrance of the cavity, and not to the metal ion as the primary sulfonamide inhibitors.

PMID:
22705188
DOI:
10.1016/j.bmc.2012.05.037
[Indexed for MEDLINE]

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