Synthesis of novel β-amino carbonyl derivatives and their inhibition effects on some metabolic enzymes

In this study, we reported the synthesis, characterization and activity-structure relationship of novel beta-amino carbonyl compounds. Some novel bis-beta-amino carbonyl (4a-e) and mono-beta-amino carbonyl (5a-e) compounds were synthesized by using CeCl3 center dot 7H(2)O catalyzed Mannich-type reaction. The title compounds were characterized by FTIR, elemental analysis, C-13 NMR and H-1 NMR techniques. In addition, the crystal and molecular structures of 5a, 5d and 5e were illuminated by single crystal X-ray diffraction. The activity-structure relationship was established by analyzing the enzyme activity of synthesized beta-amino carbonyl compounds, which were effectively inhibited by human carbonic anhydrase I (hCA I), and II (hCA II) isoenzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). According to the activity-structure relationship, the K-i values of the beta-amino carbonyl compounds were determined between 11.42 and 70.71 nM on hCA I, 28.66-77.59 nM on hCA II, 18.66-95.35 nM on AChE and 9.54 -94.70 nM on BChE. We hope that these compounds may have promising new potentials in both CA isoenzymes AChE and BChE enzyme inhibitors. (C) 2019 Elsevier B.V. All rights reserved.