Synthesis and structure-activity relationships of a new series of 2alpha-substituted trans-4,5-dimethyl-4-(3-hydroxyphenyl)piperidine as mu-selective opioid antagonists

Bertrand Le Bourdonnec; Allan J Goodman; Mathieu Michaut; Hai-Fen Ye; Thomas M Graczyk; Serge Belanger; Robert N DeHaven; Roland E Dolle

doi:10.1016/j.bmcl.2005.11.010

Synthesis and structure-activity relationships of a new series of 2alpha-substituted trans-4,5-dimethyl-4-(3-hydroxyphenyl)piperidine as mu-selective opioid antagonists

Bioorg Med Chem Lett. 2006 Feb 15;16(4):864-8. doi: 10.1016/j.bmcl.2005.11.010. Epub 2005 Nov 18.

Authors

Bertrand Le Bourdonnec¹, Allan J Goodman, Mathieu Michaut, Hai-Fen Ye, Thomas M Graczyk, Serge Belanger, Robert N DeHaven, Roland E Dolle

Affiliation

¹ Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341, USA. blebourdonnec@adolor.com

PMID: 16298525
DOI: 10.1016/j.bmcl.2005.11.010

Abstract

Structure-activity relationships at the 2alpha-position of the piperidine ring of the trans-4,5-dimethyl-4-(3-hydroxyphenyl)piperidine mu-opioid antagonist series were investigated. This study showed that only small linear alkyl groups (methyl, propyl) are tolerated at the 2alpha-position of the piperidine ring of this series.

MeSH terms

Crystallography, X-Ray
Models, Molecular
Molecular Conformation
Piperidines / chemical synthesis*
Piperidines / chemistry
Piperidines / pharmacology*
Receptors, Opioid, mu / antagonists & inhibitors*
Stereoisomerism
Structure-Activity Relationship

Substances

Piperidines
Receptors, Opioid, mu