Identification of 9-fluoro substituted (−)-cytisine derivatives as ligands with high affinity for nicotinic receptors

(−)-9-Fluorocytisine, (−)-9-methylcytisine and (−)-9-trifluoromethylcytisine were synthesized from the natural product (−)-cytisine. 9-Methyl and 9-trifluoromethyl cytisines display a remarkable affinity at the α4β2 nicotinic receptor subtype (0.2 nM) with a high selectivity versus the α7 nAChR subtype. Comparison of the affinity values suggests that the size of the substituent at the 9 position of (−)-cytisine seems more important than electronic factors for efficient binding and selectivity at α4β2 nAChRs.

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