A series of 2-azolylmethylene-3-(2H)-benzofuranone derivatives, 2-indolylmethylene-3-(2H)-benzofuranone and 2-pyrrolylmethylene-3-(2H)-benzofuranone derivatives, were synthesized, and their monoamine oxidase (MAO) A and B inhibitory activities were evaluated. Compounds 1b, 3b, 6b, 7b, and 10b showed strong inhibitory activity against MAO-A, and compound 3b showed the highest potency and selectivity, with an IC₅₀ value of 21 nM and a MAO-A selectivity index of 48. Compounds 3c, 4c, 9a, 9c, 10c, 11a, and 11c showed strong inhibitory activity against MAO-B, and compound 4c showed the highest potency and selectivity, with an IC₅₀ value of 16 nM and a MAO-B selectivity index of >1100. Further analysis of these compounds indicated that compound 3b for MAO-A and compound 4c for MAO-B were competitive inhibitors, with K_i values of 10 and 6.1 nM, respectively. Furthermore, computational analyses, such as quantitative structure–activity relationship (QSAR) analysis of the 2-azolylmethylene-3-(2H)-benzofuranone derivatives conducting their pIC₅₀ values with the Molecular Operating Environment (MOE) and Mordred, and molecular docking analysis using MOE-Dock supported that the 2-azolylmethylene-3-(2H)-benzofuranone derivatives are a privileged scaffold for the design and development of novel MAO inhibitors.

合成了一系列2-唑亚甲基-3-(2 H )-苯并呋喃酮衍生物、2-吲哚亚甲基-3-(2 H )-苯并呋喃酮和2-吡咯亚甲基-3-(2 H )-苯并呋喃酮衍生物，及其单胺评估了氧化酶 (MAO) A 和 B 的抑制活性。化合物1b、3b、6b、7b和10b对 MAO-A 显示出很强的抑制活性，化合物3b显示出最高的效力和选择性，其 IC ₅₀值为 21 nM，MAO-A 选择性指数为 48。 化合物3c、4c、9a、9c、10c、11a和11c对 MAO-B 显示出较强的抑制活性，其中化合物4c显示出最高的效力和选择性，其 IC ₅₀值为 16 nM，MAO-B 选择性指数 >1100 。对这些化合物的进一步分析表明，MAO-A 的化合物3b和MAO-B 的化合物4c是竞争性抑制剂， K _i值分别为 10 和 6.1 nM。此外，还进行计算分析，例如 2-azolymmethyl-3-(2 H )-苯并呋喃酮衍生物的定量构效关系 (QSAR) 分析，使用分子操作环境 (MOE) 和 Mordred进行 pIC ₅₀值分析，以及分子对接使用 MOE-Dock 进行的分析表明，2-唑基亚甲基-3-(2 H )-苯并呋喃酮衍生物是设计和开发新型 MAO 抑制剂的优先支架。