Discovery of novel 2,3-dihydro-1H-inden-1-amine derivatives as selective monoamine oxidase B inhibitors
Discovery of novel 2,3-dihydro-1H-inden-1-amine derivatives as selective monoamine oxidase B inhibitors
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发现新型 2,3-二氢-1H-茚-1-胺衍生物作为选择性单胺氧化酶 B 抑制剂
DOI：
10.1016/j.bmcl.2019.02.030
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发表时间：
2019-05-01
影响因子：
2.7
通讯作者：
Xie, Zhouling
中科院分区：
文献类型：
--
作者：
Li, Shiyu;Lv, Xiao;Xie, Zhouling
抑制MAO-B已成为治疗帕金森病的有效策略。为了寻找具有新型化学骨架的单胺氧化酶B抑制剂，我们在前期工作的基础上，设计合成了一系列新的2，3-二氢-1H-茚-1-胺衍生物。并对这些化合物的构效关系进行了详细的讨论。化合物L4（IC 50 = 0.11 μ M）、L 8（IC 50 = 0.18 μ M）、L16（IC 50 = 0.27 μ M）和L17（IC 50 = 0.48 μ M）显示与司来吉兰相似的MAO-B抑制活性。此外，L4、L16和L17也表现出与司来吉兰相当的选择性，表明L4、L16和L17可能是有希望的选择性单胺氧化酶B抑制剂，可用于进一步的研究。
Inhibition of MAO-B has been an effective strategy for the treatment of Parkinson's disease. To find more potent and selective MAO-B inhibitors with novel chemical scaffold, we designed and synthesized a series of new 2,3-dihydro-1H-inden-1-amine derivatives on basis of our previous study. Furthermore, the corresponding structureactivity relationship (SAR) of these compounds is detailedly discussed. Compounds L4 (IC50 = 0.11 mu M), L8 (IC50 = 0.18 mu M), L16 (IC50 = 0.27 mu M) and L17 (IC50 = 0.48 mu M) showed similar MAO-B inhibitory activity as Selegiline. Moreover, L4, L16 and L17 also exhibited comparable selectivity with Selegiline, indicating that L4, L16 and L17 could be promising selective MAO-B inhibitors for further study.