796876-15-8Relevant articles and documents
Design, syntheses, and pharmacological characterization of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3′-carboxamido)morphinan analogues as opioid receptor ligands
Yuan, Yunyun,Zaidi, Saheem A.,Stevens, David L.,Scoggins, Krista L.,Mosier, Philip D.,Kellogg, Glen E.,Dewey, William L.,Selley, Dana E.,Zhang, Yan
, p. 1701 - 1715 (2015)
A series of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3′-carboxamido)morphinan (NAQ) analogues were synthesized and pharmacologically characterized to study their structure-activity relationship at the mu opioid receptor (MOR). The competition binding assay showed two-atom spacer and aromatic side chain were optimal for MOR selectivity. Meanwhile, substitutions at the 1′- and/or 4′-position of the isoquinoline ring retained or improved MOR selectivity over the kappa opioid receptor while still possessing above 20-fold MOR selectivity over the delta opioid receptor. In contrast, substitutions at the 6′- and/or 7′-position of the isoquinoline ring reduced MOR selectivity as well as MOR efficacy. Among this series of ligands, compound 11 acted as an antagonist when challenged with morphine in warm-water tail immersion assay and produced less significant withdrawal symptoms compared to naltrexone in morphine-pelleted mice. Compound 11 also antagonized the intracellular Ca2+ increase induced by DAMGO. Molecular dynamics simulation studies of 11 in three opioid receptors indicated orientation of the 6′-nitro group varied significantly in the different 'address' domains of the receptors and played a crucial role in the observed binding affinities and selectivity. Collectively, the current findings provide valuable insights for future development of NAQ-based MOR selective ligands.
Design, synthesis, and biological evaluation of 6α- and 6β-N-heterocyclic substituted naltrexamine derivatives as μ opioid receptor selective Antagonists
Li, Guo,Aschenbach, Lindsey C.,Chen, Jianyang,Cassidy, Michael P.,Stevens, David L.,Gabra, Bichoy H.,Selley, Dana E.,Dewey, William L.,Westkaemper, Richard B.,Zhang, Yan
scheme or table, p. 1416 - 1427 (2009/12/26)
Opioid receptor selective antagonists are important pharmacological probes in opioid receptor structural characterization and opioid agonist functional study. Thus far, a nonpeptidyl, highly selective and reversible μ opioid receptor (MOR) antagonist is u
Effects of substitution on the pyrrole N atom in derivatives of tetrahydronaltrindole, tetrahydrooxymorphindole, and a related 4,5-epoxyphenylpyrrolomorphinan
Srivastava, Sanjay K.,Shefali,Miller, Carl N.,Aceto, Mario D.,Traynor, John R.,Lewis, John W.,Husbands, Stephen M.
, p. 6645 - 6648 (2007/10/03)
The effect of substitution of the pyrrolo- and indolo-N atoms in tetrahydronaltrindole (TNTI), tetrahydrooxymorphindole (TOMI), and 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-4′-phenyl-6,7:2′, 3′-pyrrolomorphinan (4) is reported. In opioid functional a
