Novel trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines as μ opioid receptor antagonists with improved opioid receptor selectivity profiles

The discovery and SAR studies of a series of N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines as novel μ opioid receptor antagonists, analogs of alvimopan, are reported. A series of N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines, μ opioid receptor antagonists, analogs...

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Veröffentlicht in:	Bioorganic & medicinal chemistry 2008-03, Vol.18 (6), p.2006-2012
Hauptverfasser:	Le Bourdonnec, Bertrand, Barker, William M., Belanger, Serge, Wiant, Daniel D., Conway-James, Nathalie C., Cassel, Joel A., O’Neill, Timothy J., Little, Patrick J., DeHaven, Robert N., DeHaven-Hudkins, Diane L., Dolle, Roland E.
Format:	Artikel
Sprache:	eng
Schlagworte:	Administration, Oral Animals Biological and medical sciences Cell Membrane - metabolism Central Nervous System - drug effects Chromatography, High Pressure Liquid Diprenorphine - metabolism Gastrointestinal Transit - drug effects Guanosine 5'-O-(3-Thiotriphosphate) - metabolism Humans Loperamide - pharmacology Medical sciences Mice Molecular Structure Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Opioid Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems Pharmacology. Drug treatments Piperidines - chemical synthesis Piperidines - chemistry Piperidines - pharmacology Receptors, Opioid, delta - antagonists & inhibitors Receptors, Opioid, delta - metabolism Receptors, Opioid, kappa - antagonists & inhibitors Receptors, Opioid, kappa - metabolism Receptors, Opioid, mu - antagonists & inhibitors Receptors, Opioid, mu - metabolism Solid phase synthesis Structure-Activity Relationship μ receptors
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Beschreibung
Zusammenfassung:	The discovery and SAR studies of a series of N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines as novel μ opioid receptor antagonists, analogs of alvimopan, are reported. A series of N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines, μ opioid receptor antagonists, analogs of alvimopan, were prepared using solid phase methodology. This study led to the identification of a highly selective μ opioid receptor antagonist, which interacts selectively with μ peripheral receptors.
ISSN:	0960-894X 0968-0896 1464-3405 1464-3391
DOI:	10.1016/j.bmcl.2008.01.106