Teodoro Rodrigo, Scheunemann Matthias, Wenzel Barbara, Peters Dan, Deuther-Conrad Winnie, Brust Peter
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Permoserstraße 15, Leipzig 04318, Germany.
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Permoserstraße 15, Leipzig 04318, Germany.
Bioorg Med Chem Lett. 2018 May 15;28(9):1471-1475. doi: 10.1016/j.bmcl.2018.03.081. Epub 2018 Mar 29.
By structure-activity relationship studies on the tilorone scaffold, the 'one armed' substituted dibenzothiophenes and the fluoren-9-ones were identified as the most potential α nAChR ligands. While the suitability of dibenzothiophene derivatives as PET tracers is recognized, the potential of fluoren-9-ones is insufficiently investigated. We herein report on a series of fluoren-9-one based derivatives targeting α nAChR with compounds 8a and 8c possessing the highest affinity and selectivity. Accordingly, with [F]8a and [F]8c we designed and initially evaluated the first fluoren-9-one derived α nAChR selective PET ligands. A future application of these radioligands is facilitated by the herein presented successful implementation of fully automated radiosynthesis.
通过对泰勒罗宁骨架的构效关系研究，确定了“单臂”取代二苯并噻吩和芴-9-酮是最具潜力的α烟碱型乙酰胆碱受体（α nAChR）配体。虽然二苯并噻吩衍生物作为正电子发射断层扫描（PET）示踪剂的适用性已得到认可，但芴-9-酮的潜力尚未得到充分研究。我们在此报告了一系列基于芴-9-酮的衍生物，它们靶向α nAChR，其中化合物8a和8c具有最高的亲和力和选择性。因此，我们设计并初步评估了首个芴-9-酮衍生的α nAChR选择性PET配体[F]8a和[F]8c。本文成功实施的全自动放射性合成促进了这些放射性配体的未来应用。
