title: Effects of N-Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Ligands.
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.
authors.affiliation: Interdepartmental Program in Medicinal Chemistry, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Aubrie A
authors.initials: AA
authors.lastname: Harland
authors.affiliation: Interdepartmental Program in Medicinal Chemistry, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Bender
authors.affiliation: Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Griggs
authors.affiliation: Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Jessica P
authors.initials: JP
authors.lastname: Anand
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Michigan , 428 Church Street, Ann Arbor, Michigan 48109, United States.
authors.forename: Irina D
authors.initials: ID
authors.lastname: Pogozheva
authors.affiliation: Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: John R
authors.initials: JR
authors.lastname: Traynor
authors.affiliation: Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Jutkiewicz
authors.affiliation: Interdepartmental Program in Medicinal Chemistry, University of Michigan , Ann Arbor, Michigan 48109, United States.|Department of Medicinal Chemistry, College of Pharmacy, University of Michigan , 428 Church Street, Ann Arbor, Michigan 48109, United States.
authors.forename: Henry I
authors.initials: HI
authors.lastname: Mosberg
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008968:Molecular Conformation; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D011804:Quinolines; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C542964:1,2,3,4-tetrahydroquinoline