- Synthesis and Characterization of Azido Aryl Analogs of IBNtxA for Radio-Photoaffinity Labeling Opioid Receptors in Cell Lines and in Mouse Brain
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Mu opioid receptors (MOR-1) mediate the biological actions of clinically used opioids such as morphine, oxycodone, and fentanyl. The mu opioid receptor gene, OPRM1, undergoes extensive alternative splicing, generating multiple splice variants. One type of splice variants are truncated variants containing only six transmembrane domains (6TM) that mediate the analgesic action of novel opioid drugs such as 3′-iodobenzoylnaltrexamide (IBNtxA). Previously, we have shown that IBNtxA is a potent analgesic effective in a spectrum of pain models but lacks many side-effects associated with traditional opiates. In order to investigate the targets labeled by IBNtxA, we synthesized two arylazido analogs of IBNtxA that allow photolabeling of mouse mu opioid receptors (mMOR-1) in transfected cell lines and mMOR-1 protein complexes that may comprise the 6TM sites in mouse brain. We demonstrate that both allyl and alkyne arylazido derivatives of IBNtxA efficiently radio-photolabeled mMOR-1 in cell lines and MOR-1 protein complexes expressed either exogenously or endogenously, as well as found in mouse brain. In future, design and application of such radio-photolabeling ligands with a conjugated handle will provide useful tools for further isolating or purifying MOR-1 to investigate site specific ligand–protein contacts and its signaling complexes.
- Grinnell, Steven G.,Uprety, Rajendra,Varadi, Andras,Subrath, Joan,Hunkele, Amanda,Pan, Ying Xian,Pasternak, Gavril W.,Majumdar, Susruta
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p. 977 - 993
(2020/05/29)
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- PROCESS FOR MAKING MORPHINAN-6alpha-OLS
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The present invention provides a process whereby morphinan-6-ones can be converted stereospecifically to the corresponding morphinan-6α-ols by catalytic hydrogenation under basic conditions.
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Page/Page column 7
(2010/03/02)
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- IMPROVED PROCESS FOR THE PREPARATION OF 6-ALPHA-HYDROXY-N-ALKYLATED OPIATES
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The present invention is directed to the conversion of a 6-keto morphinan to a 6-alpha-hydroxy morphinan in the presence of a ruthenium, rhodium, or iridium asymmetric catalyst and a hydrogen source.
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Page/Page column 25
(2009/01/20)
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- Morphine Alkaloids, Part 114 A. Stereohomogeneous Synthesis of N-Demethyl-N-Substituted-14-Hydroxydihydromorphines
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A new route for the stereohomogeneous synthesis of N-demethyl-N-substituted-14-hydroxydihydromorphines 2a-f has been elaborated, involving O-demethylation of the novel dihydrocodeine derivatives 6a-f, obtained upon alkylation of the hitherto unknown N-demethyl-14-hydroxydihydrocodeine (5). Keywords. 6α,14β-Diacetoxy-4,5α-epoxy-3-methoxy-17-methyl-morphinan, N-demethylation of; 3,6α,14β-Triacetoxy-17-alkyl-4,5α-epoxymorphinan, N-demethylation of; 17-Alkyl-4,5α-epoxy-6α,14β-dihydroxy-3-methoxymorphinan, O-demethylation of; 4,5α-Epoxy-6α,14β-dihydroxy-3-methoxymorphinan, N-alkylation of.
- Hosztafi, Sandor,Berenyi, Sandor,Toth, Geza,Makleit, Sandor
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p. 435 - 442
(2007/10/02)
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- Process for the stereoselective reduction of 6- and 8-keto morphine and morphinan derivatives with formamidinesulfinic acid and compounds obtained thereby
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Process for the stereoselective synthesis of 6β-and 8β- hydroxy epimers by the chemical reduction of 6- and 8-keto derivatives in the morphine and morphinan series utilizing alkaline formamidinesulficic acid. The 6β- and 8β-hydroxy derivatives obtained according to the invention evidence narcotic antagonist and/or agonist activity and are also useful in the chemical and pharmacological standardization of various morphine and codeine derivatives and metabolites.
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