Synthesis, biological evaluation, and SAR studies of 14?-phenylacetyl substituted 17-cyclopropylmethyl-7, 8-dihydronoroxymorphinones derivatives: Ligands with mixed NOP and opioid receptor profile

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dc.contributor.authorKumar V.
dc.contributor.authorPolgar W.E.
dc.contributor.authorCami-Kobeci G.
dc.contributor.authorThomas M.P.
dc.contributor.authorKhroyan T.V.
dc.contributor.authorToll L.
dc.contributor.authorHusbands S.M.
dc.date.accessioned2019-03-22T09:11:05Z
dc.date.accessioned2024-08-13T12:06:22Z
dc.date.available2019-03-22T09:11:05Z
dc.date.available2024-08-13T12:06:22Z
dc.date.issued2018
dc.description.abstractA series of 14?-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]GTP?S assay was partial agonism at each receptor. The results are consistent with our prediction that an appropriate 14? 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.en_US
dc.identifier.citationKumar V., Polgar W.E., Cami-Kobeci G. et.al. (2018) Synthesis, biological evaluation, and SAR studies of 14?-phenylacetyl substituted 17-cyclopropylmethyl-7, 8-dihydronoroxymorphinones derivatives: Ligands with mixed NOP and opioid receptor profileen_US
dc.identifier.doi10.3389/fpsyt.2018.00430
dc.identifier.issn16640640
dc.identifier.urihttp://10.2.3.109/handle/32116/2067
dc.language.isoenen_US
dc.publisherFrontiers Media S.A.en_US
dc.subjectAnalgesicsen_US
dc.subjectKappa opioid receptoren_US
dc.subjectMu opioid receptorsen_US
dc.subjectNociceptinen_US
dc.subjectOpioiden_US
dc.subjectORL-1en_US
dc.titleSynthesis, biological evaluation, and SAR studies of 14?-phenylacetyl substituted 17-cyclopropylmethyl-7, 8-dihydronoroxymorphinones derivatives: Ligands with mixed NOP and opioid receptor profileen_US
dc.title.journalFrontiers in Psychiatry
dc.typeArticleen_US
dc.type.accesstypeOpen Accessen_US

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