Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf
1 PublicationDevelopment of fluorinated CB2 receptor agonists for PET studies
Lueg, C.; Schepmann, D.; Günther, R.; Brust, P.; Wünsch, B.
Abstract
A convergent strategy was followed to modify systematically carbazole based CB2 receptor ligands. The length of the N-(fluoroalkyl) group (n in 7), the length of the alkanamide (m in 7) and the substitution pattern of the phenyl moiety (X and Y in 7) were varied systematically. The highest CB2 affinity was found for the 2-fluoroethyl substituted carbazole derivative 20a (Ki = 5.8 nM) containing the propionamide and the 2-bromo-4-fluorophenyl moiety. According to docking studies 20a fits nicely into the binding pocket of the CB2 receptor, but elongation of the fluoroethyl side chain leads to a different binding mode of the ligands. The high CB2 affinity together with the high selectivity over the CB2 subtype qualifies the fluoroethyl derivative 20a to be developed as a PET tracer.
Keywords: CB2 receptor ligands; Carbazole derivatives; Fluorinated ligands; Structure affinity relationships; PET; Docking
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Bioorganic & Medicinal Chemistry 21(2013), 7481-7498
DOI: 10.1016/j.bmc.2013.09.040
Cited 22 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-19376