trans-3,4-dimethyl-4-(3-carboxamidophenyl)piperidines: a novel class of micro-selective opioid antagonists.
trans-3,4-Dimethyl-4-(3-carboxamidophenyl)piperidines constitute a novel class of micro opioid receptor antagonists. The CONH(2) group was found to be an effective isostere of the phenolic OH moiety. Structure-activity relationships at the piperidine nitrogen position led to the identification of several ligands displaying high affinity toward the cloned human micro opioid receptors, good selectivity micro/delta, micro/kappa, and potent in vitro antagonist activity.
Le Bourdonnec
Bertrand
B
Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341, USA. blebourdonnec@adolor.com
Belanger
Serge
S
Cassel
Joel A
JA
Stabley
Gabriel J
GJ
DeHaven
Robert N
RN
Dolle
Roland E
RE
D001667:Binding, Competitive; D003001:Cloning, Molecular; D004174:Diprenorphine / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D010880:Piperidines; D017450:Receptors, Opioid, mu; D011994:Recombinant Proteins; D004174:Diprenorphine