New 3-[4-(aryl)piperazin-1-yl]-1-(benzo[b]thiophen-2-yl)propane derivatives with dual action at 5-HT1A serotonin receptors and serotonin transporter as a new class of antidepressants.
Some benzo[b]thiophene derivatives with different substituents in positions 3 and 5 have been synthesized in order to obtain new dual antidepressant drugs. Compounds derived from 2-acetyl-3-methylbenzo[b]thiophene or 2-acetyl-3,5-dimethylbenzo[b]thiophene were prepared with two different phenylpiperazines (2-methoxy and 2-hydroxyphenylpiperazine) and evaluated for in vitro 5-HT1A receptor affinity and serotonin reuptake inhibition by radioligand assays. Compound 1-(3,5-dimethylbenzo[b]thiophen-2-yl)-3-[4-(2-methoxyphenyl)piperazin-1- yl]propan-1-ol (II.2.a) shows good values (nM) for both activities: Ki = 85 for 5-HT1A receptor and Ki = 120 for serotonin transporter.
Department of Medicinal Chemistry, Centro de Investigación en Farmacobiología Aplicada CIFA, Universidad de Navarra, Pamplona, Spain.
L
L
Orús
Y
Y
Sáinz
S
S
Pérez
A M
AM
Oficialdegui
J
J
Martinez
B
B
Lasheras
J
J
del Río
A
A
Monge
D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000378:metabolism; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011407:Propane / Q000031:analogs & derivatives* / Q000737:chemistry; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D018490:Serotonin Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins; D013055:Spectrophotometry, Infrared; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*
D000928:Antidepressive Agents; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D013876:Thiophenes; D011407:Propane