title: Novel trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines as mu opioid receptor antagonists with improved opioid receptor selectivity profiles.
abstract: A series of N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines, mu opioid receptor antagonists, analogs of alvimopan, were prepared using solid phase methodology. This study led to the identification of a highly selective mu opioid receptor antagonist, which interacts selectively with mu peripheral receptors.
authors.affiliation: Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341, USA. blebourdonnec@adolor.com
authors.forename: Bertrand
authors.initials: B
authors.lastname: Le Bourdonnec
authors.forename: William M
authors.initials: WM
authors.lastname: Barker
authors.forename: Serge
authors.initials: S
authors.lastname: Belanger
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Wiant
authors.forename: Nathalie C
authors.initials: NC
authors.lastname: Conway-James
authors.forename: Joel A
authors.initials: JA
authors.lastname: Cassel
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: O'Neill
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Little
authors.forename: Robert N
authors.initials: RN
authors.lastname: DeHaven
authors.forename: Diane L
authors.initials: DL
authors.lastname: DeHaven-Hudkins
authors.forename: Roland E
authors.initials: RE
authors.lastname: Dolle
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004174:Diprenorphine / Q000378:metabolism; D005772:Gastrointestinal Transit / Q000187:drug effects; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D008139:Loperamide / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C485764:OPRM1 protein, human; D010880:Piperidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D004174:Diprenorphine; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C419502:alvimopan; D008139:Loperamide