Design and synthesis of some new benzoylthioureido phenyl derivatives targeting carbonic anhydrase enzymes

Abstract

The present study aimed to develop potent carbonic anhydrase inhibitors (CAIs). The design of the target compounds was based on modifying the structure of the ureido-based carbonic anhydrase inhibitor SLC-0111. Six series of a substituted benzoylthioureido core were prepared featuring different zinc-binding groups; the conventional sulphamoyl group 4a–d and 12a–c, its bioisosteric carboxylic acid group 5a–d and 13a–c or the ethyl carboxylate group 6a–d and 14a–c as potential prodrugs. All compounds were assessed for their carbonic anhydrase (CA) inhibitory activity against a panel of four physiologically relevant human CA isoforms hCA I and hCA II, and hCA IX, and hCA XII. Compounds 4a, 4b, 4c, 4d, 5d, 12a, and 12c revealed significant inhibitory activity against hCA I that would highlight these compounds as promising drug candidates for the treatment of glaucoma.

Keywords:

• Sulphonamides
• carbonic anhydrase
• SLC-0111
• benzoylthioureido derivatives

Disclosure statement

C. T. Supuran is Editor-in-Chief of the Journal of Enzyme Inhibition and Medicinal Chemistry and he was not involved in the assessment, peer review, or decision-making process of this paper. The authors have no relevant affiliations of financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Additional information

Funding

This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. C. T. Supuran and D. Vullo thank the Italian Ministry for University and Research (MIUR), for the project FISR2019_04819 BacCAD with which this research was funded.