title: Evaluation of structurally diverse neuronal nicotinic receptor ligands for selectivity at the alpha6( *) subtype.
abstract: Direct comparison of pyridine versus pyrimidine substituents on a small but diverse set of ligands indicates that the pyrimidine substitution has the potential to enhance affinity and/or functional activity at alpha6 subunit-containing neuronal nicotinic receptors (NNRs) and decrease activation of ganglionic nicotinic receptors, depending on the scaffold. The ramifications of this structure-activity relationship are discussed in the context of the design of small molecules targeting smoking cessation.
authors: Department of Medicinal Chemistry, Targacept, Inc., 200 East First St., Suite 300, Winston-Salem, NC 27101, USA.
authors: Scott R
authors: SR
authors: Breining
authors: Merouane
authors: M
authors: Bencherif
authors: Sharon R
authors: SR
authors: Grady
authors: Paul
authors: P
authors: Whiteaker
authors: Michael J
authors: MJ
authors: Marks
authors: Charles R
authors: CR
authors: Wageman
authors: Henry A
authors: HA
authors: Lester
authors: Daniel
authors: D
authors: Yohannes
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004298:Dopamine / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008956:Models, Chemical; D009538:Nicotine / Q000737:chemistry; D010300:Parkinson Disease / Q000188:drug therapy; D011485:Protein Binding; D011743:Pyrimidines / Q000737:chemistry; D011978:Receptors, Nicotinic / Q000737:chemistry*; D016540:Smoking Cessation / Q000379:methods*; D013329:Structure-Activity Relationship
chemical_list: C470410:CHRNA6 protein, human; D008024:Ligands; D011743:Pyrimidines; D011978:Receptors, Nicotinic; D009538:Nicotine; D004298:Dopamine