796876-15-8Relevant academic research and scientific papers
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.
POTENT AND SELECTIVE MU OPIOID RECEPTOR MODULATORS
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Page/Page column 18; 31; 32, (2017/12/18)
Analogues of 6 α/β-naltrexamine (NAQ) are provided. The analogues are selective, reversible antagonists of the mu opioid receptor (MOR) that exhibit good blood brain barrier penetration. The compounds are used in the treatment of opioid addiction and other diseases and conditions, including for the treatment of pain.
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
Extension of the Nenitzescu reaction to simple ketones provides an efficient route to 1′-alkyi-5′-hydroxynaltrindole analogues, potent and selective δ-opioid receptor antagonists
Shefali,Srivastava, Sanjay K.,Husbands, Stephen M.,Lewis, John W.
, p. 635 - 638 (2007/10/03)
The well-established Nenitzescu reaction of imines of β-dicarbonyl systems, as their enamine tautomers, with benzoquinone has been applied to a wide range of such imines to give 5-hydroxyindoles, some of which are of significant biological importance. Thi
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
4'-Arylpyrrolomorphinans: effect of a pyrrolo-N-benzyl substituent in enhancing delta-opioid antagonist activity.
Srivastava, Sanjay K,Husbands, Stephen M,Aceto, Mario D,Miller, Carl N,Traynor, John R,Lewis, John W
, p. 537 - 540 (2007/10/03)
A new method for the preparation of N-benzylpyrrolomorphinans has been developed. Thus Michael reaction of the benzylimines of oxycodones and oxymorphones with nitrostyrenes gave a series of 4'-aryl-N-benzylpyrrolomorphinans. These were selective delta an
