2-[4-[3-(4-aryl/heteroaryl-1-piperazinyl)propoxy]phenyl]-2H- benzotriazoles 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-benzo tri azoles and corresponding N-oxides were prepared. The synthesized compounds were able to bind on some serotonin (5-HT1A, 5-HT2A) and dopamine (D2, D3) receptors, while displaying poor or no affinity for 5-HT1B, 5-HT2C, 5-HT3, and 5-HT4 subtypes. The strong contribution of the N-oxide function for the binding on 5-HT1A, D2 and D3 receptors is noteworthy. For 2-{4-[3-[4-(2-methoxyphenyl)-1-piperazinyl]propoxy]phenyl}-2H-benzotr iazole- 1-oxide (4b), the binding constants (Ki) were 11.9 (5-HT1A) 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.