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

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 37; no. 1; pp. 2702 - 2709
• Main Authors: Najm, Mazin A. A., Mahmoud, Walaa R., Taher, Azza T., Abbas, Safinaz E-S., Awadallah, Fadi M., Allam, Heba Abdelrasheed, Vullo, Daniela, Supuran, Claudiu T.
• Format: Journal Article
• Language: English
• Published: Abingdon Taylor & Francis 31-12-2022; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Acids; Alzheimer's disease; benzoylthioureido derivatives; Carbon; carbonic anhydrase; Carbonic anhydrases; Carboxylic acids; Drug development; Enzymes; Functional foods & nutraceuticals; Glaucoma; Isoforms; Organic chemistry; Pharmaceuticals; Pharmacy; Research Paper; SLC-0111; Sulphonamides
• ISSN: 1475-6366; 1475-6374
• DOI: 10.1080/14756366.2022.2126463

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.