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

Nicolas Houllier; JaganMohan Gopisetti; Pierre Lestage; Marie-Claire Lasne; Jacques Rouden

doi:10.1016/j.bmcl.2010.09.017

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

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6667-70. doi: 10.1016/j.bmcl.2010.09.017. Epub 2010 Sep 15.

Authors

Nicolas Houllier¹, JaganMohan Gopisetti, Pierre Lestage, Marie-Claire Lasne, Jacques Rouden

Affiliation

¹ 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.

PMID: 20880707
DOI: 10.1016/j.bmcl.2010.09.017

Abstract

(-)-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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkaloids / chemistry
Alkaloids / metabolism*
Azocines / chemistry
Azocines / metabolism
Fluorine / chemistry*
Ligands
Quinolizines / chemistry
Quinolizines / metabolism
Radioligand Assay
Receptors, Nicotinic / metabolism*

Substances

Alkaloids
Azocines
Ligands
Quinolizines
Receptors, Nicotinic
Fluorine
cytisine