In the attempt to define more accurately structure-affinity relationships for ó1 and ó2 ligands,we synthesized and tested on ó subtype receptors a series of aralkyl derivatives of 4-benzylpiperidine,in which the effect of modifications on the aralkyl moiety was studied in a systematicway. The affinity of the compounds here described varied to a great extent, with a ó2/ó1selectivity ranging from 0.1 to 9. Thus, to confirm the ability of the piperazine derivative tobind to ó1 receptors in a different way than piperidines, we synthesized and tested a series ofpiperazine compounds; the comparison of their affinity with that of the correspondingpiperidines strongly supports the possibility of a different binding mode. While the compoundshere described are on the whole selective for ó vs serotonin 5-HT1A and dopamine D2 receptors,9aa, 9ba and 9ab possess a remarkable affinity for both ó and 5-HT1A receptors, with Ki inthe nanomolar range, and are selective with respect to D2 receptors. They displayed also apartial agonist profile in a human 5-HT1A [35S]GTPçS binding assay, suggesting their potentialuse as atypical antipsychotic agents.

Synthesis and structure-activity relationships of 1-aralkyl-4- benzylpiperidine and 1-aralkyl-4-benzylpiperazine derivatives as potent σ ligands / Costantino, Luca; Gandolfi, Francesca; Sorbi, Claudia; Franchini, Silvia; Prezzavento, O; Vittorio, F; Ronsisvalle, G; Leopardi, A; Poggesi, E; Brasili, Livio. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 48:1(2005), pp. 266-273. [10.1021/jm049433t]

Synthesis and structure-activity relationships of 1-aralkyl-4- benzylpiperidine and 1-aralkyl-4-benzylpiperazine derivatives as potent σ ligands

COSTANTINO, Luca;GANDOLFI, Francesca;SORBI, Claudia;FRANCHINI, Silvia;BRASILI, Livio
2005

Abstract

In the attempt to define more accurately structure-affinity relationships for ó1 and ó2 ligands,we synthesized and tested on ó subtype receptors a series of aralkyl derivatives of 4-benzylpiperidine,in which the effect of modifications on the aralkyl moiety was studied in a systematicway. The affinity of the compounds here described varied to a great extent, with a ó2/ó1selectivity ranging from 0.1 to 9. Thus, to confirm the ability of the piperazine derivative tobind to ó1 receptors in a different way than piperidines, we synthesized and tested a series ofpiperazine compounds; the comparison of their affinity with that of the correspondingpiperidines strongly supports the possibility of a different binding mode. While the compoundshere described are on the whole selective for ó vs serotonin 5-HT1A and dopamine D2 receptors,9aa, 9ba and 9ab possess a remarkable affinity for both ó and 5-HT1A receptors, with Ki inthe nanomolar range, and are selective with respect to D2 receptors. They displayed also apartial agonist profile in a human 5-HT1A [35S]GTPçS binding assay, suggesting their potentialuse as atypical antipsychotic agents.
2005
48
1
266
273
Synthesis and structure-activity relationships of 1-aralkyl-4- benzylpiperidine and 1-aralkyl-4-benzylpiperazine derivatives as potent σ ligands / Costantino, Luca; Gandolfi, Francesca; Sorbi, Claudia; Franchini, Silvia; Prezzavento, O; Vittorio, F; Ronsisvalle, G; Leopardi, A; Poggesi, E; Brasili, Livio. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 48:1(2005), pp. 266-273. [10.1021/jm049433t]
Costantino, Luca; Gandolfi, Francesca; Sorbi, Claudia; Franchini, Silvia; Prezzavento, O; Vittorio, F; Ronsisvalle, G; Leopardi, A; Poggesi, E; Brasili, Livio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/610724
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