Novel 1-phenylpiperazine and 4-phenylpiperidine derivatives as high-affinity sigma ligands.
J Med Chem
; 34(12): 3360-5, 1991 Dec.
Article
en En
| MEDLINE
| ID: mdl-1662725
ABSTRACT
sigma receptors may represent an exciting new approach for the development of novel psychotherapeutic agents. Unfortunately, many of the commonly used sigma ligands lack selectivity (e.g., many bind at phencyclidine or dopamine receptors) or suffer from other serious drawbacks. Recently, we described a series of 2-phenylaminoethanes that bind at sigma receptors with high affinity and selectivity. Because there is evidence that 1-phenylpiperazines can structurally mimic the 2-phenylaminoethane moiety, we prepared a series of 1-phenylpiperazines and related analogues and incorporated structural features already shown to enhance the sigma binding of the 2-phenylaminoethanes. Several of these derivatives bind at sigma receptors with high affinity (Ki = 1-10 nM) and lack appreciable affinity for phencyclidine and dopamine receptors. In as much as certain of these agents structurally resemble the high-affinity, but nonselective, sigma ligand haloperidol, and because they bind with 10 times the affinity of haloperidol, we have apparently identified what appears to be the primary sigma pharmacophore of that agent.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piperazinas
/
Piperidinas
/
Receptores Opioides
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
1991
Tipo del documento:
Article