ICTM-Department of Chemistry, University of Belgrade, Njegoševa 12, 11000 Belgrade, Serbia.
Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Research Site Leipzig, Permoserstraße 15, 04318 Leipzig, Germany.
Molecules. 2020 Oct 26;25(21):4941. doi: 10.3390/molecules25214941.
Herein, we report on the synthesis and pharmacological evaluation of ten novel fluorinated cinnamylpiperazines as potential monoamine oxidase B (MAO-B) ligands. The designed derivatives consist of either cinnamyl or 2-fluorocinnamyl moieties connected to 2-fluoropyridylpiperazines. The three-step synthesis starting from commercially available piperazine afforded the final products in overall yields between 9% and 29%. An in vitro competitive binding assay using l-[H]Deprenyl as radioligand was developed and the MAO-B binding affinities of the synthesized derivatives were assessed. Docking studies revealed that the compounds - were stabilized in both MAO-B entrance and substrate cavities, thus resembling the binding pose of l-Deprenyl. Although our results revealed that the novel fluorinated cinnamylpiperazines - do not possess sufficient MAO-B binding affinity to be eligible as positron emission tomography (PET) agents, the herein developed binding assay and the insights gained within our docking studies will certainly pave the way for further development of MAO-B ligands.
在此，我们报告了十种新型氟代肉桂基哌嗪的合成和药理学评价，这些化合物作为潜在的单胺氧化酶 B（MAO-B）配体。设计的衍生物由肉桂基或 2-氟肉桂基部分连接到 2-氟吡啶基哌嗪上。从商业可得的哌嗪开始的三步合成以 9％至 29％的总产率得到最终产物。开发了一种使用 l-[H]Deprenyl 作为放射性配体的体外竞争性结合测定法，并评估了合成衍生物的 MAO-B 结合亲和力。对接研究表明，化合物 - 在 MAO-B 入口和底物腔中均稳定，因此类似于 l-Deprenyl 的结合构象。尽管我们的结果表明，新型氟代肉桂基哌嗪 - 不具有足够的 MAO-B 结合亲和力作为正电子发射断层扫描（PET）剂，但在此开发的结合测定法和我们的对接研究中获得的见解肯定将为 MAO-B 配体的进一步开发铺平道路。
