title: N-(Imidazolidin-2-ylidene)-1-arylmethanamine oxides: synthesis, structure and pharmacological evaluation.
abstract: A high yielding three-step procedure was applied for the synthesis of N-(imidazolidin-2-ylidene)-1-arylmethanamine oxides 3 (α-aminonitrones) starting from the easily accessible imidazolidin-2-one O-benzyl oxime 1. The α-aminonitrone-α-iminohydroxyloamine tautomerism of these products was studied theoretically and the structures of the synthesised compounds were confirmed by single crystal X-ray crystallographic analysis. The compounds were evaluated in vitro for their binding affinities to α(1)  and α(2)  adrenoceptors as well as imidazoline I(1)  and I(2)  receptors. The highest potencies at the α(2)  adrenergic receptors were observed for compounds bearing biphenyl (4h, K(i)  = 9 nM) and naphthyl (4i, K(i)  = 92 nM) moieties. Compounds 4h and 4i were further tested in vivo for their cardiovascular and sedative-hypnotic effects in rats.
authors.affiliation: Department of Chemical Technology of Drugs, Medical University of Gdansk, Gdańsk, Poland. js@gumed.edu.pl
authors.forename: Jarosław
authors.initials: J
authors.lastname: Saczewski
authors.forename: Alan
authors.initials: A
authors.lastname: Hudson
authors.forename: Shayna
authors.initials: S
authors.lastname: Laird
authors.forename: Apolonia
authors.initials: A
authors.lastname: Rybczyńska
authors.forename: Konrad
authors.initials: K
authors.lastname: Boblewski
authors.forename: Artur
authors.initials: A
authors.lastname: Lehmann
authors.forename: Daqing
authors.initials: D
authors.lastname: Ma
authors.forename: Mervyn
authors.initials: M
authors.lastname: Maze
authors.forename: Helena
authors.initials: H
authors.lastname: Watts
authors.forename: Maria
authors.initials: M
authors.lastname: Gdaniec
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic; D018360:Crystallography, X-Ray; D015195:Drug Design; D006898:Hydroxylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054755:Imidazoline Receptors / Q000378:metabolism; D048288:Imidazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D010087:Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D006898:Hydroxylamines; D054755:Imidazoline Receptors; D048288:Imidazolines; D010087:Oxides; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; C410887:imidazoline I1 receptors; C487767:imidazoline receptor 2