Synthesis and alpha-adrenergic binding ligand affinities of 2-iminoimidazolidine derivatives.
In order to obtain possible veinotonic drugs acting through alpha2 receptor activation, we prepared clonidine analogues in which the 2-imino-imidazolidine was attached to various aliphatic or aromatic heterocycles. Among them, the two benzopyranic derivatives 16 and 22 exhibited interesting affinities (19 and 95 nM respectively on [3H]rauwolscine binding, compared to 35 nM for clonidine). Their affinity for alpha1 receptors was found to be much lower: 7570 and 5030 nM for 16 and 22 respectively, suggesting 16 to be 400 times more selective for alpha2 than for alpha1-adrenoceptors.
Chang-Fong
J
J
Groupe de Pharmacochimie Moléculaire, UMR 5063-CNRS, Faculté de Pharmacie, Université J. Fourier, La Tronche, France.
Benamour
K
K
Szymonski
B
B
Thomasson
F
F
Morand
J M
JM
Cussac
M
M
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D003000:Clonidine / Q000378:metabolism; D019329:Idazoxan / Q000031:analogs & derivatives / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D015016:Yohimbine / Q000378:metabolism
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D008024:Ligands; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; C058525:2-methoxyidazoxan; D003000:Clonidine; D011224:Prazosin; D019329:Idazoxan