2-(4,5-Dihydroimidazol-2-yl)benzimidazoles as highly selective imidazoline I2/adrenergic alpha2 receptor ligands.
2-(4,5-Dihydroimidazol-2-yl)benzimidazoles have been identified as selective imidazoline I2/alpha2-adrenoceptor ligands. 4-Methyl (2) and 4-chloro (4) derivatives display I2 affinity at nanomolar concentration (Ki=4.4 and 17.7 nM, respectively) and high I2/alpha2 selectivity ratio=4226 and 5649, respectively. An evidence has been obtained that pKa value influences considerably the I2/alpha2-selectivity ratio of this class of imidazoline I2 receptor ligands.
Saczewski
Francieszek
F
Department of Chemical Technology of Drugs, Medical University of Gdańsk, 80-416 Gdańsk, Poland. saczew@amg.gda.pl
Tabin
Piotr
P
Tyacke
Robin J
RJ
Maconie
Alys
A
Saczewski
Jarosław
J
Kornicka
Anita
A
Nutt
David J
DJ
Hudson
Alan L
AL
D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D004583:Electrons; D054755:Imidazoline Receptors; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008024:Ligands; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D011955:Receptors, Drug / Q000187:drug effects*; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D054755:Imidazoline Receptors; D007202:Indicators and Reagents; D008024:Ligands; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; C487767:imidazoline receptor 2