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Stereochemical basis for a unified structure activity theory of aromatic and heterocyclic rings in selected opioids and opioid peptides.

dc.contributor.author Goldberg, Joel S
dc.date.accessioned 2019-08-07T16:52:18Z
dc.date.available 2019-08-07T16:52:18Z
dc.date.issued 2010-02-18
dc.identifier.issn 1177-391X
dc.identifier.issn 1177-391X
dc.identifier.uri https://hdl.handle.net/10161/19174
dc.description.abstract This paper presents a novel unified theory of the structure activity relationship of opioids and opioid peptides. It is hypothesized that a virtual or known heterocyclic ring exists in all opioids which have activity in humans, and this ring occupies relative to the aromatic ring of the drug, approximately the same plane in space as the piperidine ring of morphine. Since the rings of morphine are rigid, and the aromatic and piperidine rings are critical structural components for morphine's analgesic properties, the rigid morphine molecule allows for approximations of the aromatic and heterocyclic relationships in subsequent drug models where bond rotations are common. This hypothesis and five propositions are supported by stereochemistry and experimental observations.Proposition #1 The structure of morphine provides a template. Proposition #2 Steric hindrance of some centric portion of the piperidine ring explains antagonist properties of naloxone, naltrexone and alvimopam. Proposition #3 Methadone has an active conformation which contains a virtual heterocyclic ring which explains its analgesic activity and racemic properties. Proposition #4 The piperidine ring of fentanyl can assume the morphine position under conditions of nitrogen inversion. Proposition #5 The first 3 amino acid sequences of beta endorphin (l-try-gly-gly) and the active opioid dipeptide, l-tyr-pro, (as a result of a peptide turn and zwitterion bonding) form a virtual piperazine-like ring which is similar in size, shape and location to the heterocyclic rings of morphine, meperidine, and methadone. Potential flaws in this theory are discussed.This theory could be important for future analgesic drug design.
dc.language eng
dc.publisher SAGE Publications
dc.relation.ispartof Perspectives in medicinal chemistry
dc.relation.isversionof 10.4137/pmc.s3898
dc.subject analgesic
dc.subject heterocyclic
dc.subject opioid
dc.subject stereochemistry
dc.title Stereochemical basis for a unified structure activity theory of aromatic and heterocyclic rings in selected opioids and opioid peptides.
dc.type Journal article
duke.contributor.id Goldberg, Joel S|0011931
dc.date.updated 2019-08-07T16:52:17Z
pubs.begin-page 1
pubs.end-page 10
pubs.issue 4
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Anesthesiology, VA Anesthesiology Service
pubs.organisational-group Anesthesiology
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
pubs.volume 4


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