2-Azolylchromone Derivatives as Potent and Selective Inhibitors of Monoamine Oxidases A and B.

A series of 2-azolylchromone derivatives were synthesized and their monoamine oxidase (MAO) A and B inhibitory activities were evaluated. Of the synthesized compounds, compounds 1b, 2b, 4a-c, 5b and 7b showed potent inhibitory activities against MAO-A (IC50 values, 1b: 0.32 µM; 2b: 0.14 µM; 4a: 0.11 µM; 4b: 0.023 µM; 4c: 0.15 µM; 5b: 0.59 µM; 7b: 0.19 µM) and 4a, c, 5a, c, 6c and 8c for MAO-B (IC50 values, 4a: 0.028 µM; 4c: 0.019 µM; 5a: 0.73 µM; 5c: 0.28 µM; 6c: 0.28 µM; 8c: 0.27 µM). These data suggest that 6-methoxy substitution favors MAO-A inhibition and 7-methoxy substitution favors MAO-B inhibition. In addition, compound 4b was the most potent inhibitor for MAO-A, and compound 4c for MAO-B. This is the first report identifying 2-azolylchromone derivatives as potent monoamine oxidase inhibitors. These results suggest that the 2-triazolylchromone structure may be a useful scaffold for the design and development of novel monoamine oxidase inhibitors, as evidenced by the activities of 4a-c and 5a-c.