Synthesis and radiofluorination of novel fluoren-9-one based derivatives for the imaging of α7 nicotinic acetylcholine receptor with PET. Issue 9 (15th May 2018)

• Record Type: Journal Article
• Authors: Teodoro, Rodrigo; Scheunemann, Matthias; Wenzel, Barbara; Peters, Dan; Deuther-Conrad, Winnie; Brust, Peter
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 9(2018)
• Page Start: 1471
• Page End: 1475
• Publication Date: 2018-05-15
• Subjects: α7 nAChR -- PET -- Radiofluorination -- Fluoren-9-one -- Dibenzothiophenes; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.03.081
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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 α7 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 α7 nAChR with compounds 8a and 8c possessing the highest affinity and selectivity. Accordingly, with [ 18 F]8a and [ 18 F]8c we designed and initially evaluated the first fluoren-9-one derived α7 nAChR selective PET ligands. A future application of these radioligands is facilitated by the herein presented successful implementation of fully automated radiosynthesis.