Design and synthesis of new benzimidazole-arylpiperazine derivatives acting as mixed 5-HT1A/5-HT3 ligands.
A series of new benzimidazole-arylpiperazine derivatives III were designed, synthesized and evaluated for binding affinity at serotoninergic 5-HT(1A) and 5-HT(3) receptors. Compound IIIc was identified as a novel mixed 5-HT(1A)/5-HT(3) ligand with high affinity for both serotonin receptors and excellent selectivity over alpha(1)-adrenergic and dopamine D(2) receptors. This compound was characterized as a partial agonist at 5-HT(1A)Rs and a 5-HT(3)R antagonist, and was effective in preventing the cognitive deficits induced by muscarinic receptor blockade in a passive avoidance learning test.
López-Rodríguez
María L
ML
Departamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense, E-28040 Madrid, Spain. mluzlr@quim.ucm.es
Benhamú
Bellinda
B
Morcillo
Maria José
MJ
Tejada
Ignacio
I
Avila
David
D
Marco
Isabel
I
Schiapparelli
Lucio
L
Frechilla
Diana
D
Del Río
Joaquín
J
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D015195:Drug Design; D008024:Ligands; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*
D001562:Benzimidazoles; D008024:Ligands; D010879:Piperazines; D044406:Receptors, Serotonin, 5-HT3; D044282:Receptor, Serotonin, 5-HT1A