Synthesis of N′-phenyl-N-hydroxyureas and investigation of their inhibitory activities on human carbonic anhydrases

[Display omitted] •N′-phenyl-N-hydroxyureas were reported as inhibitors of human carbonic anhydrases.•The 22 compounds were assayed as inhibitors of hCA I, II, IX and XII.•Some compounds showed selectivity against tumor associated hCA IX and XII.•Compounds 13, 21 and 22 were the most potent inhibitors of the series. A series of N′-phenyl-N-hydroxyureas has been prepared by reacting hydroxylamine with aromatic isocyanates. These compounds were investigated as inhibitors of human carbonic anhydrases (hCAs, EC 4.2.1.1), considering four physiologically relevant isoforms, the cytosolic isoforms hCA I and II, and tumor associated, transmembrane isoforms hCA IX and XII. The new compounds reported here did not inhibit the widespread cytosolic isoforms hCA I and II, but they inhibited the tumor associated isoforms with interesting potencies. The most effective inhibitors showed KIs ranging between 72.8 and 78.9 nM against hCA IX and between 6.9 and 7.2 against hCA XII, making them of interest as candidates for antitumor studies.