The therapeutic indications for monoamine oxidases A and B (MAO-A and MAO-B) inhibitors that have emerged from biological studies on animal and cellular models of neurological and oncological diseases have focused drug discovery projects upon identifying reversible MAO inhibitors. Screening of our in-house academic compound library identified two hit compounds that inhibit MAO-B with IC₅₀ values in micromolar range. Two series of indole (23 analogues) and 3-(benzyloxy)benzyl)piperazine (16 analogues) MAO-B inhibitors were derived from hits, and screened for their structure-activity relationships. Both series yielded low micromolar selective inhibitors of human MAO-B, namely indole 2 (IC₅₀ = 12.63 ± 1.21 µM) and piperazine 39 (IC₅₀ = 19.25 ± 4.89 µM), which is comparable to selective MAO-B inhibitor isatin (IC₅₀ = 6.10 ± 2.81 µM), yet less potent in comparison to safinamide (IC₅₀ = 0.029 ± 0.002 µM). Selective MAO-B inhibitors 2, 14, 38 and 39 exhibited favourable permeation of the blood-brain barrier and low cytotoxicity in the human neuroblastoma cell line SH-SY5Y.

单胺氧化酶 A 和 B（MAO-A 和 MAO-B）抑制剂的治疗适应症来自对神经和肿瘤疾病的动物和细胞模型的生物学研究，已将药物发现项目集中在识别可逆的 MAO 抑制剂上。对我们内部学术化合物库的筛选确定了两种抑制 MAO-B 的热门化合物，IC ₅₀值在微摩尔范围内。两个系列的吲哚（23 个类似物）和 3-（苄氧基）苄基）哌嗪（16 个类似物）MAO-B 抑制剂来源于命中，并筛选了它们的构效关系。这两个系列均产生了低微摩尔选择性人 MAO-B 抑制剂，即吲哚2 (IC ₅₀ = 12.63 ± 1.21 µM) 和哌嗪39 (IC ₅₀ = 19.25 ± 4.89 µM)，与选择性 MAO-B 抑制剂 isatin (IC _{50 = 6.10 ± 2.81 µM) 相当，但与 safinamide (IC 50} = 0.029 ± 0.002 µM)相比效力较低。选择性 MAO-B 抑制剂2、14、38和39在人神经母细胞瘤细胞系 SH-SY5Y 中表现出良好的血脑屏障渗透性和低细胞毒性。