2-(4,5-Dihydro-1H-imidazol-2-yl)indazole (indazim) derivatives as selective I2 imidazoline receptor ligands

Abstract

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 I2 receptors and α2-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 [3H]2BFI-labeled imidazoline I2 receptors relative to the [ 3H]RX821001-labeled α2-adrenergic receptors. This highly selective compound should prove to be useful tool in further understanding the functions of the imidazoline I2 receptors. © 2003 Elsevier B.V. All rights reserved.