Optimization of (arylpiperazinylbutyl)oxindoles exhibiting selective 5-HT7 receptor antagonist activity.
J Med Chem
; 54(19): 6657-69, 2011 Oct 13.
Article
em En
| MEDLINE
| ID: mdl-21859099
A series of (arylpiperazinylbutyl)oxindoles as highly potent 5-HT(7) receptor antagonists has been studied for their selectivity toward the 5-HT(1A) receptor and α(1)-adrenoceptor. Several derivatives exhibited high 5-HT(7)/5-HT(1A) selectivity, and the key structural factors for reducing undesired α(1)-adrenergic receptor binding have also been identified. Rapid metabolism, a common problem within this family of compounds, could be circumvented with appropriate substitution patterns on the oxindole carbocycle. Contrary to expectations, none of the compounds produced an antidepressant-like action in the forced swimming test in mice despite sufficiently high brain concentrations. On the other hand, certain analogues showed significant anxiolytic activity in two different animal models: the Vogel conflict drinking test in rats and the light-dark test in mice.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piperazinas
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Antagonistas da Serotonina
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Ansiolíticos
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Receptores de Serotonina
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Indóis
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Antidepressivos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article