Identification of a new scaffold for opioid receptor antagonism based on the 2-amino-1,1-dimethyl-7-hydroxytetralin pharmacophore.
J Med Chem
; 47(21): 5069-75, 2004 Oct 07.
Article
em En
| MEDLINE
| ID: mdl-15456250
ABSTRACT
The trans-(3,4)-dimethyl-4-(3-hydroxyphenyl)piperidines are a unique class of opioid antagonists that have recently provided selective antagonists for mu-opioid receptors (MOR) and kappa-opioid receptors (KOR). Molecular modeling indicated a strong structural similarity between the parent of this series and 2-amino-1,1-dimethyl-7-hydroxytetralin. In binding and in vitro functional assays, the aminotetralin derivatives displayed some overlap in SAR with that previously reported for the phenylpiperidine series, providing evidence for a common binding mode for the two series at opioid receptors. Introduction of a methoxy group in the 3-position increased potency at MOR and KOR receptors, suggesting that this aminotetralin skeleton can be utilized as a new scaffold for the design of selective opioid receptor antagonists.
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Base de dados:
MEDLINE
Assunto principal:
Tetra-Hidronaftalenos
/
Receptores Opioides kappa
/
Receptores Opioides mu
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article