2-(4,5-dihydro-1H-imidazol-2-yl)indazole (indazim) derivatives as selective I(2) imidazoline receptor ligands.
A series of variously substituted 2-(4,5-dihydro-1H-imidazol-2-yl)indazoles 3a-j and 2-(4,5-dihydro-1H-imidazol-2-yl)-4,5,6,7-tetrahydroindazole 6 were prepared by the regiospecific heteroalkylation of corresponding indazoles 1a-k with 2-chloro-4,5-dihydroimidazole (2). Their affinity to imidazoline I(2) receptors and alpha(2)-adrenergic receptors was determined by radioligand binding assay carried out on P(2) membrane preparations obtained from rat whole brains. 4-Chloro-2-(4,5-dihydro-1H-imidazol-2-yl)indazole (3f, 4-Cl-indazim) showed a 3076-fold difference in affinity for the [(3)H]2BFI-labeled imidazoline I(2) receptors relative to the [(3)H]RX821001-labeled alpha(2)-adrenergic receptors. This highly selective compound should prove to be useful tool in further understanding the functions of the imidazoline I(2) receptors.
Saczewski
F
F
Department of Chemical Technology of Drugs, Medical University of Gdańsk, Al Gen Hallera 107, 80-416 Gdańsk, Poland. saczew@sanus.amg.gda.pl
Hudson
A L
AL
Tyacke
R J
RJ
Nutt
D J
DJ
Man
J
J
Tabin
P
P
Saczewski
J
J
D000818:Animals; D001572:Benzofurans / Q000737:chemistry; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000737:chemistry; D054755:Imidazoline Receptors; D066298:In Vitro Techniques; D007211:Indoles / Q000737:chemistry; D054833:Isoindoles; D008024:Ligands; D008297:Male; D008958:Models, Molecular; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D011955:Receptors, Drug / Q000187:drug effects*
D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D007211:Indoles; D054833:Isoindoles; D008024:Ligands; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; C097364:4-chloro-2-(imidazolin-2-yl)isoindoline; C103723:2-(2-benzofuranyl)-2-imidazoline