title: Synthesis and activity of 3-pyridylamine ligands at central nicotinic receptors.
abstract: A series of thirty 2-(3-pyridylaminomethyl)azetidine, pyrrolidine and piperidine analogues as nicotinic acetylcholine receptor (nAChR) ligands was explored. In general, pyrrolidinyl and many azetidinyl compounds were found to bind with enhanced affinity relative to the piperidines. In the three series, the parallel structural changes (stereochemistry, N-methylation and/or chloro substitution) do not consistently lead to parallel shifts in affinity. The more active compounds (K(i) affinity values ranging from 8.9 to 90 nM) were about as analgesic as nicotine in a tail-flick assay in mice after subcutaneous injections.
authors.affiliation: Dipartimento di Tossicologia dell'Università di Cagliari, Ferrara, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Balboni
authors.forename: M
authors.initials: M
authors.lastname: Marastoni
authors.forename: S
authors.initials: S
authors.lastname: Merighi
authors.forename: P
authors.initials: P
authors.lastname: Andrea Borea
authors.forename: R
authors.initials: R
authors.lastname: Tomatis
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D008024:Ligands; D008297:Male; D051379:Mice; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000588:Amines; D000700:Analgesics; D008024:Ligands; D011725:Pyridines; D011978:Receptors, Nicotinic; C023666:pyridine