New 3-[4-(2,3-dihydro-14-benzodioxin-5-yl)piperazin-1-yl]-1-(5-substituted benzo[b]thiophen-3-yl)propanol derivatives with dual action at 5-HT(1A) serotonin receptors and serotonin transporter as a new class of antidepressants.
Compounds derived from 2,3-dihydro-(1,4-benzodioxin-5-yl)piperazine and benzo[b]thiophene with different substituents in 5 position (H, F, NO2, NH2, CH3 and OH) have been synthesized in order to obtain new dual antidepressant drugs. The final compounds were evaluated for in vitro 5-HT(1A) receptor affinity and serotonin reuptake inhibition by radioligand assays. Compounds 1-(5-nitrobenzo[b]thiophen-3-yl)-3-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]propan-1-ol (4c) (Ki = 6.8 for 5-HT(1A) receptor and Ki = 14 for 5-HT transporter) and 1-(5-hydroxybenzo[b]thiophen-3-yl)-3-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl] propan-1-ol (4f) (Ki = 6.2 for 5-HT(1A) receptor and Ki = 18.2 for 5-HT transporter) showed the best results for both activities.
Department of Medicinal Chemistry and Centro de Investigación en Farmacobiología Aplicada, Universidad de Navarra, Pamplona, Spain.
S Perez
SP
Silanes
L
L
Orús
A M
AM
Oficialdegui
J
J
Martínez Esparza
B
B
Lasheras
J
J
Del Río
A
A
Monge
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000138:chemical synthesis* / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000187:drug effects*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000187:drug effects*; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D020005:Propanols / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D050486:Serotonin Plasma Membrane Transport Proteins; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry
D018687:Antidepressive Agents, Second-Generation; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; D020005:Propanols; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D013876:Thiophenes; D044282:Receptor, Serotonin, 5-HT1A