Autor: |
Martı´nez, Javier, Pe´rez, Silvia, Oficialdegui, Ana M., Heras, Begon˜a, Oru´s, Lara, Villanueva, Helena, Palop, Juan A., Roca, Joan, Mourelle, Marisa, Bosch, Ana, Castillo, Juan-C. Del, Lasheras, Berta, Tordera, Rosa, Rı´o, Joaquı´n del, Monge, Antonio |
Zdroj: |
European Journal of Medicinal Chemistry; 2001, Vol. 36 Issue: 1 p55-61, 7p |
Abstrakt: |
A series of new 3-[4-(aryl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propane derivatives were synthesized in an attempt to find a new class of antidepressant drugs with dual activity at 5-HT 1A serotonin receptors and serotonin transporter. Title compounds were evaluated for in vitro activity on 5-HT 1A receptor and 5-HT transporter. They show high nanomolar affinity for both activities, and in particular, compounds 1-(5-chlorobenzo[b]thiophen-3-yl)-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-ol ( 7 ) and 1-(5-fluorobenzo[b]thiophen-3-yl)-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-ol ( 8 ) show values (nM) of K i =30 and 2.3 for 5-HT 1A receptors and K i =30 and 12 for serotonin transporters, respectively. In GTPγS binding assays, compound 8 revealed antagonist properties to 5-HT 1A receptors. Such a pharmacological profile could lead to potent antidepressant agents with new dual mechanism of action. |
Databáze: |
Supplemental Index |
Externí odkaz: |
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