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Sixteen compounds (<b>TR1–TR16</b>) were synthesized and evaluated for their inhibitory activities against monoamine oxidase A and B (MAOs). Most of the derivatives showed potent and highly selective MAO-B inhibition. Compound <b>TR16</b> was the most potent inhibitor against MAO-B with an IC₅₀ value of 0.17 μM, followed by <b>TR2</b> (IC₅₀ = 0.27 μM). <b>TR2</b> and <b>TR16</b> selectivity index (SI) values for MAO-B versus MAO-A were 84.96 and higher than 235.29, respectively. Compared to the basic structures, the <i>para</i>-chloro substituent in <b>TR2</b> and <b>TR16</b> increased the inhibitory activity of MAO-B. <b>TR2</b> and <b>TR16</b> were reversible MAO-B inhibitors that were competitive, with K_i values of 0.230 ± 0.004 and 0.149 ± 0.016 µM, respectively. The PAMPA method indicated that compounds <b>TR2</b> and <b>TR16</b> had the tendency to traverse the blood–brain barrier. Docking investigations revealed that lead compounds were beneficial for MAO-B inhibition via association with key as well as selective E84 or Y326 residues, but not for MAO-A inhibition via interaction primarily driven by hydrophobic contacts. In conclusion, TR2 and TR16 are therapeutic prospects for the management of multiple neurodegenerative diseases.