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

Reference:

Grundt, P., Williams, I. A., Lewis, J. W. and Husbands, S. M., 2004. Identification of a new scaffold for opioid receptor antagonism based on the 2-amino-1,1-dimethyl-7-hydroxytetralin pharmacophore. Journal of Medicinal Chemistry, 47 (21), pp. 5069-5075.

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Official URL:

http://dx.doi.org/10.1021/jm040807s

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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