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Identification of a new scaffold for opioid receptor antagonism based on the 2-amino-1,1-dimethyl-7-hydroxytetralin pharmacophore.

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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Grundt P,Williams IA,Lewis JW,Husbands SM

doi

10.1021/jm040807s

keywords:

subject

Has Abstract

pub_date

2004-10-07 00:00:00

pages

5069-75

issue

21

eissn

0022-2623

issn

1520-4804

journal_volume

47

pub_type

杂志文章

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