title: New aromatic iminoimidazolidine derivatives as alpha1-adrenoceptor antagonists: a novel synthetic approach and pharmacological activity.
abstract: The design, synthesis and alpha1-adrenoceptor antagonism of a series of bis-imidazoline (1a, 2a, 3a and 4a) and bis-guanidine (1b, 2b, 3b and 4b) diphenyl derivatives are reported. All of these compounds fulfill the conditions of the most recent pharmacophore proposed for alpha1-adrenoceptors and found in the literature. Besides, a novel synthetic approach to the preparation of 2-(arylimino)imidazolidine derivatives is described. All the tested compounds, except the bis-guanidinium derivative 3b, inhibit the contractile responses induced by noradrenaline in aortic rings of rat and rabbit in a dose-dependent manner. Our results indicate that, even though some discrepancies are observed in terms of the alpha1 subtype targeted by this new family of compounds, they show an interesting profile as antagonists of alpha1-adrenoceptors and a new prototype, compound 1a, has been found deserving further development.
authors.affiliation: Instituto de Química Médica (CSIC), Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Dardonville
authors.forename: P
authors.initials: P
authors.lastname: Goya
authors.forename: I
authors.initials: I
authors.lastname: Rozas
authors.forename: A
authors.initials: A
authors.lastname: Alsasua
authors.forename: M I
authors.initials: MI
authors.lastname: Martín
authors.forename: M J
authors.initials: MJ
authors.lastname: Borrego
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D019791:Guanidine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007097:Imines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008297:Male; D008958:Models, Molecular; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D007097:Imines; D011942:Receptors, Adrenergic, alpha; D014662:Vasoconstrictor Agents; C014973:2-aminoimidazole; D019791:Guanidine; D001920:Bradykinin; D009638:Norepinephrine