Fluorinated pyrrolidines and piperidines incorporating tertiary benzenesulfonamide moieties are selective carbonic anhydrase II inhibitors

Abstract

A series of substituted pyrrolidines and piperidines were synthesized using superacid HF/SbF₅ chemistry. Investigated as inhibitors of several human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, i.e. the cytosolic hCA I and II as well as the tumor-associated transmembrane isoforms hCA IX and XII, these compounds showed a never yet reported selectivity toward the human carbonic anhydrase hCA II. In the tertiary benzenesulfonamide family, this class of inhibitors points out a new mechanism of action for human carbonic anhydrase II inhibition.

• Carbonic anhydrase
• fluorine
• selectivity
• superacid
• tertiary benzenesulfonamides

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. We are indebted to the Université de Poitiers, the CNRS, @rtMolecule and ANRT (CIFRE scholarship for A.LD) and an EU FP7 grant (Dynano to CTS) for financial support.