title: Cytisine derivatives as high affinity nAChR ligands: synthesis and comparative molecular field analysis.
abstract: A number of new N-substituted cytisine derivatives were prepared and tested, along with similar compounds already described by us and others, as high affinity neuronal acetylcholine receptor ligands. Structure-affinity relationships were discussed in the light of our recently proposed pharmacophore model for nicotinic receptor agonists. The most significant physicochemical interactions modulating the receptor-ligand binding were detected at the three dimensional (3D) level by means of comparative molecular field analysis (CoMFA). The best predictive PLS model was a single-field steric model showing good statistical figures: n = 17, Q2 = 0.717, s(ev) = 0.566, r2 = 0.942, s = 0.275.
authors.affiliation: Dipartimento Farmaco Chimico, Università degli Studi, Bari, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Nicolotti
authors.forename: C
authors.initials: C
authors.lastname: Canu Boido
authors.forename: F
authors.initials: F
authors.lastname: Sparatore
authors.forename: A
authors.initials: A
authors.lastname: Carotti
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001392:Azocines; D002540:Cerebral Cortex / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D021281:Quantitative Structure-Activity Relationship; D011807:Quinolizines; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013223:Statistics as Topic; D000093843:Quinolizidine Alkaloids
chemical_list: D000470:Alkaloids; D001392:Azocines; D008024:Ligands; D011807:Quinolizines; D011978:Receptors, Nicotinic; C004712:cytisine; D000093843:Quinolizidine Alkaloids