Diels-Alder Adducts of Morphinan-6,8-Dienes and Their Transformations.

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)

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:

17 May 2022 10:41

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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