| 15634021 |
Costantino L, Gandolfi F, Sorbi C, Franchini S, Prezzavento O, Vittorio F, Ronsisvalle G, Leonardi A, Poggesi E, Brasili L: Synthesis and structure-activity relationships of 1-aralkyl-4-benzylpiperidine and 1-aralkyl-4-benzylpiperazine derivatives as potent sigma ligands. J Med Chem. 2005 Jan 13;48(1):266-73.
In the attempt to define more accurately structure-affinity relationships for sigma (1) and sigma (2) ligands, we synthesized and tested on sigma subtype receptors a series of aralkyl derivatives of 4-benzylpiperidine, in which the effect of modifications on the aralkyl moiety was studied in a systematic way. The affinity of the compounds here described varied to a great extent, with a sigma (2)/sigma (1) selectivity ranging from 0.1 to 9. Thus, to confirm the ability of the piperazine derivative to bind to sigma (1) receptors in a different way than piperidines, we synthesized and tested a series of piperazine compounds; the comparison of their affinity with that of the corresponding piperidines strongly supports the possibility of a different binding mode. While the compounds here described are on the whole selective for sigma vs serotonin 5-HT (1A) and dopamine D (2) receptors, 9aa, 9ba and 9ab possess a remarkable affinity for both sigma and 5-HT (1A) receptors, with K (i) in the nanomolar range, and are selective with respect to D (2) receptors. They displayed also a partial agonist profile in a human 5-HT (1A) [(35) S] GTP gamma S binding assay, suggesting their potential use as atypical antipsychotic agents. |
2(0,0,0,2) |