Novel and selective 5-HT2C/2B receptor antagonists as potential anxiolytic agents: synthesis, quantitative structure-activity relationships, and molecular modeling of substituted 1-(3-pyridylcarbamoyl)indolines.
J Med Chem
; 41(10): 1598-612, 1998 May 07.
Article
em En
| MEDLINE
| ID: mdl-9572885
The synthesis, biological activity, and molecular modeling of a novel series of substituted 1-(3-pyridylcarbamoyl)indolines are reported. These compounds are isosteres of the previously published indole urea 1 (SB-206553) and illustrate the use of aromatic disubstitution as a replacement for fused five-membered rings in the context of 5-HT2C/2B receptor antagonists. By targeting a region of space previously identified as sterically allowed at the 5-HT2C receptor but disallowed at the 5-HT2A receptor, we have identified a number of compounds which are the most potent and selective 5-HT2C/2B receptor antagonists yet reported. 46 (SB-221284) was selected on the basis of its overall biological profile for further evaluation as a novel, potential nonsedating anxiolytic agent. A CoMFA analysis of these compounds produced a model with good predictive value and in addition good qualitative agreement with both our 5-HT2C receptor model and our proposed binding mode for this class of ligands within that model.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridinas
/
Antagonistas da Serotonina
/
Ansiolíticos
/
Modelos Moleculares
/
Receptores de Serotonina
/
Indóis
Tipo de estudo:
Prognostic_studies
/
Qualitative_research
Limite:
Animals
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Reino Unido