Synthesis, biological evaluation, and SAR studies of 14β-phenylacetyl substituted 17-cyclopropylmethyl-7, 8-dihydronoroxymorphinones derivatives: Ligands with mixed NOP and opioid receptor profile
Polgar, Willma E.
Thomas, Mark P.
Khroyan, Taline V.
Husbands, Stephen M.
AffiliationCentral University of Punjab
University of Bath
Florida Atlantic University
SubjectsMu opioid receptors
Kappa opioid receptor,
Subject Categories::B200 Pharmacology, Toxicology and Pharmacy
MetadataShow full item record
AbstractA series of 14β-acyl substituted 17-cyclopropylmethyl-7,8-dihydronoroxymorphinone compounds has been synthesized and evaluated for affinity and efficacy for mu (MOP), kappa (KOP), and delta (DOP) opioid receptors and nociceptin/orphanin FQ peptide (NOP) receptors. The majority of the new ligands displayed high binding affinities for the three opioid receptors, and moderate affinity for NOP receptors. The affinities for NOP receptors are of particular interest as most classical opioid ligands do not bind to NOP receptors. The predominant activity in the [35S]GTPγS assay was partial agonism at each receptor. The results are consistent with our prediction that an appropriate 14β side chain would access a binding site within the NOP receptor and result in substantially higher affinity than displayed by the parent compound naltrexone. Molecular modeling studies, utilizing the recently reported structure of the NOP receptor, are also consistent with this interpretation.
CitationKumar V, Polgar WE, Cami-Kobeci G, Thomas MP, Khroyan TV, Toll L, Husbands SM (2018) 'Synthesis, biological evaluation, and SAR studies of 14β-phenylacetyl substituted 17-cyclopropylmethyl-7, 8-dihydronoroxymorphinones derivatives: Ligands with mixed NOP and opioid receptor profile', Frontiers in Psychiatry, 9, pp.430-.
PublisherFrontiers Media S.A.
JournalFrontiers in Psychiatry
PubMed Central IDPMC6156383
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International
- Discovery of the first small-molecule opioid pan antagonist with nanomolar affinity at mu, delta, kappa, and nociceptin opioid receptors.
- Authors: Zaveri NT, Journigan VB, Polgar WE
- Issue date: 2015 Apr 15
- Mu-opioid peptide (MOP) and nociceptin/orphanin FQ peptide (NOP) receptor activation both contribute to the discriminative stimulus properties of cebranopadol in the rat.
- Authors: Tzschentke TM, Rutten K
- Issue date: 2018 Feb
- Pharmacogenomic study of the role of the nociceptin/orphanin FQ receptor and opioid receptors in diabetic hyperalgesia.
- Authors: Rutten K, Tzschentke TM, Koch T, Schiene K, Christoph T
- Issue date: 2014 Oct 15
- Nociceptin/orphanin FQ receptor activation attenuates antinociception induced by mixed nociceptin/orphanin FQ/mu-opioid receptor agonists.
- Authors: Khroyan TV, Polgar WE, Jiang F, Zaveri NT, Toll L
- Issue date: 2009 Dec
- Designing bifunctional NOP receptor-mu opioid receptor ligands from NOP-receptor selective scaffolds. Part II.
- Authors: Journigan VB, Polgar WE, Khroyan TV, Zaveri NT
- Issue date: 2014 Apr 15