title: Methylation of imidazoline related compounds leads to loss of α₂-adrenoceptor affinity. Synthesis and biological evaluation of selective I₁ imidazoline receptor ligands.
abstract: Methylated analogues of imidazoline related compounds (IRC) were prepared; their abilities to bind I(1) imidazoline receptors (I(1)Rs), I(2) imidazoline binding sites (I(2)BS) and α(2)-adrenoceptor subtypes (α(2)ARs) were assessed. Methylation of the heterocyclic moiety of IRC resulted in a significant loss of α(2)AR affinity. Amongst the selective ligands obtained, LNP 630 (4) constitutes the first highly selective I(1)R agent showing hypotensive activity after intravenous administration.
authors: Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, EA 4438, Université de Strasbourg, Faculté de Médecine, 11, rue Humann, F-67000 Strasbourg, France. sschann@domaintherapeutics.com
authors: Stephan
authors: S
authors: Schann
authors: Hugues
authors: H
authors: Greney
authors: Vincent
authors: V
authors: Gasparik
authors: Monique
authors: M
authors: Dontenwill
authors: Carla
authors: C
authors: Rascente
authors: Gabriel
authors: G
authors: Lacroix
authors: Laurent
authors: L
authors: Monassier
authors: Véronique
authors: V
authors: Bruban
authors: Josiane
authors: J
authors: Feldman
authors: Jean-Daniel
authors: JD
authors: Ehrhardt
authors: Pascal
authors: P
authors: Bousquet
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D054755:Imidazoline Receptors / Q000737:chemistry* / Q000378:metabolism; D048288:Imidazolines / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D007275:Injections, Intravenous; D008024:Ligands; D008297:Male; D008745:Methylation; D015394:Molecular Structure; D016716:PC12 Cells; D051381:Rats; D011918:Rats, Inbred SHR; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D054755:Imidazoline Receptors; D048288:Imidazolines; D008024:Ligands; D018341:Receptors, Adrenergic, alpha-2; C410887:imidazoline I1 receptors; C487767:imidazoline receptor 2