Marton, János; Fekete, Anikó; Cumming, Paul; Hosztafi, Sándor; Mikecz, Pál; Henriksen, Gjermund (2022). Diels-Alder Adducts of Morphinan-6,8-Dienes and Their Transformations. Molecules, 27(9) Molecular Diversity Preservation International MDPI 10.3390/molecules27092863
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6,14-ethenomorphinans are semisynthetic opiate derivatives containing an ethylene bridge between positions 6 and 14 in ring-C of the morphine skeleton that imparts a rigid molecular structure. These compounds represent an important family of opioid receptor ligands in which the 6,14-etheno bridged structural motif originates from a [4 + 2] cycloaddition of morphinan-6,8-dienes with dienophiles. Certain 6,14-ethenomorphinans having extremely high affinity for opioid receptors are often non-selective for opioid receptor subtypes, but this view is now undergoing some revision. The agonist 20R-etorphine and 20R-dihydroetorphine are several thousand times more potent analgesics than morphine, whereas diprenorphine is a high-affinity non-selective antagonist. The partial agonist buprenorphine is used as an analgesic in the management of post-operative pain or in substitution therapy for opiate addiction, sometimes in combination with the non-selective antagonist naloxone. In the context of the current opioid crisis, we communicated a summary of several decades of work toward generating opioid analgesics with lesser side effects or abuse potential. Our summary placed a focus on Diels-Alder reactions of morphinan-6,8-dienes and subsequent transformations of the cycloadducts. We also summarized the pharmacological aspects of radiolabeled 6,14-ethenomorphinans used in molecular imaging of opioid receptors.
Item Type: |
Journal Article (Review Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine |
UniBE Contributor: |
Cumming, Paul |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1420-3049 |
Publisher: |
Molecular Diversity Preservation International MDPI |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
17 May 2022 10:32 |
Last Modified: |
05 Dec 2022 16:19 |
Publisher DOI: |
10.3390/molecules27092863 |
PubMed ID: |
35566212 |
Uncontrolled Keywords: |
Diels–Alder reaction Grignard addition O-demethylation morphinan-6,8-dienes morphine alkaloids opioid receptors positron emission tomography radiolabeling |
BORIS DOI: |
10.48350/170041 |
URI: |
https://boris.unibe.ch/id/eprint/170041 |
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