title: Synthesis and biological evaluation of pyridine-modified analogues of 3-(2-aminoethoxy)pyridine as novel nicotinic receptor ligands.
abstract: Analogues of the potent nicotinic receptor agonist 3-(2-aminoethoxy)pyridine substituted at the 5' and 6'-positions of the pyridine ring were synthesized and tested in vitro for nicotinic receptor binding activity (displacement of [(3)H](-)cytisine from whole rat brain synaptic membranes). The substituted analogues exhibited K(i) values ranging from 0.076 to 319 nM compared to a K(i) value of 26 nM for compound 1. Among the compounds tested, 5'-vinyl-6'-chloro substituted 1 was the most potent.
authors.affiliation: Neurological and Urological Diseases Research, D-47W, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA. nanhorng.lin@abbott.com
authors.forename: Nan-Horng
authors.initials: NH
authors.lastname: Lin
authors.forename: Liming
authors.initials: L
authors.lastname: Dong
authors.forename: William H
authors.initials: WH
authors.lastname: Bunnelle
authors.forename: David J
authors.initials: DJ
authors.lastname: Anderson
authors.forename: Michael D
authors.initials: MD
authors.lastname: Meyer
mesh_terms: D000818:Animals; D001921:Brain / Q000648:ultrastructure; D008024:Ligands; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013570:Synaptic Membranes / Q000378:metabolism
chemical_list: C116733:3-(2-(pyrrolidinyl)methoxy)pyridine; C475588:3-(2-aminoethoxy)pyridine; D008024:Ligands; D018722:Nicotinic Agonists; D011725:Pyridines; D011759:Pyrrolidines; D011978:Receptors, Nicotinic