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.
Sparatore
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Istituto di Chimica Farmaceutica e Tossicologica, Università di Milano, Italy. sparator@imiucca.csi.unimi.it
Goegan
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Cagnotto
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Sparatore
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F
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018491:Dopamine Agonists / Q000378:metabolism; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009830:Olfactory Bulb / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D018490:Serotonin Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013134:Spiperone / Q000378:metabolism; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000378:metabolism; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D015259:Dopamine Agents; D018491:Dopamine Agonists; D008024:Ligands; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D013764:Tetrahydronaphthalenes; D014230:Triazoles; D013134:Spiperone; C031349:7-hydroxy-2-N,N-dipropylaminotetralin