Abstract
N-Acetylation of the tetrahydroquinoline (THQ) core of a series of μ-opioid receptor (MOR) agonist/δ-opioid receptor (DOR) antagonist ligands increases DOR affinity, resulting in ligands with balanced MOR and DOR affinities. We report a series of N-substituted THQ analogues that incorporate various carbonyl-containing moieties to maintain DOR affinity and define the steric and electronic requirements of the binding pocket across the opioid receptors. 4h produced in vivo antinociception (ip) for 1 h at 10 mg/kg.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Animals
-
Cell Line, Tumor
-
Dose-Response Relationship, Drug
-
Ligands
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Models, Molecular
-
Molecular Conformation
-
Quinolines / chemical synthesis
-
Quinolines / chemistry*
-
Quinolines / pharmacology*
-
Rats
-
Receptors, Opioid, delta / antagonists & inhibitors*
-
Receptors, Opioid, mu / agonists*
-
Structure-Activity Relationship
Substances
-
Ligands
-
Quinolines
-
Receptors, Opioid, delta
-
Receptors, Opioid, mu
-
1,2,3,4-tetrahydroquinoline