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Twelve pyridazinones (<b>T1</b>–<b>T12</b>) containing the (2-fluorophenyl) piperazine moiety were designed, synthesized, and evaluated for monoamine oxidase (MAO) -A and -B inhibitory activities. <b>T6</b> was found to be the most potent MAO-B inhibitor with an IC₅₀ value of 0.013 µM, followed by <b>T3</b> (IC₅₀ = 0.039 µM). Inhibitory potency for MAO-B was more enhanced by <i>meta</i> bromo substitution (<b>T6</b>) than by <i>para</i> bromo substitution (<b>T7</b>). For <i>para</i> substitution, inhibitory potencies for MAO-B were as follows: -Cl (<b>T3</b>) > -N(CH₃)₂ (<b>T12</b>) > -OCH₃ (<b>T9</b>) > Br (<b>T7</b>) > F (<b>T5</b>) > -CH₃ (<b>T11</b>) > -H (<b>T1</b>). <b>T6</b> and <b>T3</b> efficiently inhibited MAO-A with IC₅₀ values of 1.57 and 4.19 µM and had the highest selectivity indices (SIs) for MAO-B (120.8 and 107.4, respectively). <b>T3</b> and <b>T6</b> were found to be reversible and competitive inhibitors of MAO-B with K_i values of 0.014 and 0.0071, respectively. Moreover, <b>T6</b> was less toxic to healthy fibroblast cells (L929) than <b>T3</b>. Molecular docking simulations with MAO binding sites returned higher docking scores for <b>T6</b> and <b>T3</b> with MAO-B than with MAO-A. These results suggest that <b>T3</b> and <b>T6</b> are selective, reversible, and competitive inhibitors of MAO-B and should be considered lead candidates for the treatment of neurodegenerative disorders like Alzheimer’s disease.