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 α(4)β(2) nicotinic receptor subtype (0.2 nM) with a high selectivity versus the α(7) 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 α(4)β(2) nAChRs.
Houllier
Nicolas
N
Laboratoire de Chimie Moléculaire et Thioorganique, UMR 6507 CNRS, ENSICAEN-Université de Caen Basse-Normandie, Institut Normand de Chimie Moléculaire, Médicinale et Macromoléculaire FR 3038 CNRS, 6 Boulevard du Maréchal Juin, 14050 Caen, France.
Gopisetti
JaganMohan
J
Lestage
Pierre
P
Lasne
Marie-Claire
MC
Rouden
Jacques
J
D000470:Alkaloids / Q000737:chemistry / Q000378:metabolism*; D001392:Azocines / Q000737:chemistry / Q000378:metabolism; D005461:Fluorine / Q000737:chemistry*; D008024:Ligands; D011807:Quinolizines / Q000737:chemistry / Q000378:metabolism; D011869:Radioligand Assay; D011978:Receptors, Nicotinic / Q000378:metabolism*; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D001392:Azocines; D005461:Fluorine; D008024:Ligands; D011807:Quinolizines; D011978:Receptors, Nicotinic; C004712:cytisine; D000093843:Quinolizidine Alkaloids