2-{4-[3-(4-Aryl/heteroaryl-1-piperazinyl)propoxy]phenyl}-2H-benzotriaz-oles and their N-oxides as ligands for serotonin and dopamine receptors

A small set of 2-{4-[3-(4-aryl/heteroaryl-piperazinyl)propoxy]phenyl}-2H-benzotriazoles and corresponding N-oxides were prepared. The synthesized compounds were able to bind on some serotonin (5-HT(1A), 5-HT(2A)) and dopamine (D₂, D₃) receptors, while displaying poor or no affinity for 5-HT(1B), 5-HT(2C), 5-HT₃, and 5-HT₄ subtypes. The strong contribution of the N-oxide function for the binding on 5-HT(1A), D₂ and D₃ receptors is noteworthy. For 2-{4-[3-[4-(2-methoxyphenyl)-1-piperazinyl]propoxy]phenyl}-2H-benzotriazol-1 -oxide (4b), the binding constants (K(i)) were 11.9 (5-HT(1A)) and 10.5 nM (D₃). In a general pharmacological screening, the 2-(4-[3-(4-phenyl-1-piperazinyl)propoxy]phenyl}-2H-benzotriazole (3a) exhibited only very weak activities, with the exception of protecting mice from cyanide-induced hypoxia.