Novel trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines as mu opioid receptor antagonists with improved opioid receptor selectivity profiles.
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.
Le Bourdonnec
Bertrand
B
Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341, USA. blebourdonnec@adolor.com
Barker
William M
WM
Belanger
Serge
S
Wiant
Daniel D
DD
Conway-James
Nathalie C
NC
Cassel
Joel A
JA
O'Neill
Timothy J
TJ
Little
Patrick J
PJ
DeHaven
Robert N
RN
DeHaven-Hudkins
Diane L
DL
Dolle
Roland E
RE
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
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