Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

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 (K_i = 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.