Effects of N-Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Ligands

Autor:	Chao Gao, Henry I. Mosberg, Nicholas W. Griggs, John R. Traynor, Aaron M. Bender, Emily M. Jutkiewicz, Irina D. Pogozheva, Jessica P. Anand, Aubrie A. Harland
Rok vydání:	2016
Předmět:	0301 basic medicine Steric effects Agonist Male Models Molecular Stereochemistry medicine.drug_class Molecular Conformation Receptors Opioid mu Ligands 01 natural sciences Article 03 medical and health sciences Mice Structure-Activity Relationship In vivo Opioid receptor Cell Line Tumor Receptors Opioid delta Drug Discovery medicine Animals Receptor Dose-Response Relationship Drug 010405 organic chemistry Chemistry Antagonist Affinities Combinatorial chemistry 3. Good health 0104 chemical sciences Rats Mice Inbred C57BL 030104 developmental biology Opioid Quinolines Molecular Medicine medicine.drug
Zdroj:	Journal of Medicinal Chemistry
ISSN:	1520-4804
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::28aa24f12d4288bfccf2f67e3b7752ea https://pubmed.ncbi.nlm.nih.gov/27148755 Zobrazit plný text záznamu