4-Phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives, a novel class of selective delta-opioid agonists.
A novel series of 4-phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives has been prepared and their synthesis described herein. In vitro affinities for delta-, mu-, and kappa-opioid receptors, as well as the functional activity in the [(35)S]GTPgammaS assay are reported. The most potent and selective delta-opioid agonist 18a exhibited a K(i) of 18 nM, and was >258-fold and 28-fold selective over mu- and kappa-receptors, respectively; the compound is a full agonist with an EC(50) value of 14 nM.
Trabanco
Andrés A
AA
Division of Psychiatry, Research and Early Development Europe, Johnson and Johnson Pharmaceutical Research and Development, Jarama 75, 47007 Toledo, Spain. atrabanc@prdes.jnj.com
Pullan
Shirley
S
Alonso
José M
JM
Alvarez
Rosa M
RM
Andrés
José I
JI
Boeckx
Inge
I
Fernández
Javier
J
Gómez
Antonio
A
Iturrino
Laura
L
Janssens
Frans E
FE
Leenaerts
Joseph E
JE
De Lucas
Ana I
AI
Matesanz
Encarna
E
Meert
Theo
T
Steckler
Thomas
T
D001667:Binding, Competitive; D015195:Drug Design; D004345:Drug Industry / Q000379:methods*; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000819:agonists*; D013329:Structure-Activity Relationship
C508741:4-phenyl-4-(1H-imidazol-2-yl)piperidine; D007093:Imidazoles; D010455:Peptides; D010880:Piperidines; D017465:Receptors, Opioid, delta; C032727:piperidine