New 3-[4-(3-substituted phenyl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propanol derivatives with dual action at 5-HT1A serotonin receptors and serotonin transporter as a new class of antidepressants.
In this paper a series of new 3-[4-(3-substituted phenyl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propanol derivatives is presented as a new class of antidepressant drugs with dual activity at 5-HT1A serotonin receptors and serotonin transporter. The 5-HT1A receptor and 5-HT transporter binding affinities of hydroxylic compounds 4 a-e have been determined. The new compounds present nanomolar affinity for both activities, and 1-(benzo[b]thiophen-3-yl)-3-[4-(3-methoxyphenyl)piperazin-1-yl]propan-1-ol (4d) shows values (nM) of Ki = 86 for 5-HT1A receptors and Ki = 76 for the serotonin transporter, respectively.
Orús
L
L
Department of Medicinal Chemistry, Centro de Investigación en Farmacobiología Aplicada, Universidad de Navarra, Pamplona, Spain.
Martínez
J
J
Pérez
S
S
Oficialdegui
A M
AM
del Castillo
J C
JC
Mourelle
M
M
Lasheras
B
B
del Río
J
J
Monge
A
A
D018687:Antidepressive Agents, Second-Generation / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D002352:Carrier Proteins / Q000187:drug effects*; D007202:Indicators and Reagents; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000187:drug effects*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D020005:Propanols / Q000737:chemistry*; D011485:Protein Binding; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D050486:Serotonin Plasma Membrane Transport Proteins; D013876:Thiophenes / Q000737:chemistry*
C466143:3-(4-(3-phenyl)piperazin-1-yl)-1-(benzo(b)thiophen-3-yl)propanol; D018687:Antidepressive Agents, Second-Generation; D002352:Carrier Proteins; D007202:Indicators and Reagents; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D020005:Propanols; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D050486:Serotonin Plasma Membrane Transport Proteins; D013876:Thiophenes