Oxa-adamantyl cannabinoids.

Cannabinoids / chemistry Dose-Response Relationship, Drug Humans Molecular Structure Receptor, Cannabinoid, CB1 / agonists Receptor, Cannabinoid, CB2 / agonists Structure-Activity Relationship
Binding affinity CB1 cannabinoid receptor CB2 cannabinoid receptor Classical cannabinoid Design Hexahydrocannabinol Novel class Oxa-adamantyl cannabinoid Synthesis

Journal

Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377

Informations de publication

Date de publication:
15 04 2021
Historique:
received: 11 11 2020
revised: 01 01 2021
accepted: 12 02 2021
pubmed: 27 2 2021
medline: 26 8 2021
entrez: 26 2 2021
Statut: ppublish

Résumé

As a continuation of earlier work on classical cannabinoids bearing bulky side chains we report here the design, synthesis, and biological evaluation of 3'-functionalized oxa-adamantyl cannabinoids as a novel class of cannabinergic ligands. Key synthetic steps involve nucleophilic addition/transannular cyclization of aryllithium to epoxyketone in the presence of cerium chloride and stereoselective construction of the tricyclic cannabinoid nucleus. The synthesis of the oxa-adamantyl cannabinoids is convenient, and amenable to scale up allowing the preparation of these analogs in sufficient quantities for detailed in vitro evaluation. The novel oxa-adamantyl cannabinoids reported here were found to be high affinity ligands for the CB1 and CB2 cannabinoid receptors. In the cyclase assay these compounds were found to behave as potent and efficacious CB1 receptor agonists. Isothiocyanate analog AM10504 is capable of irreversibly labeling both the CB1 and CB2 receptors.

Identifiants

DOI: 10.1016/j.bmcl.2021.127882 PMID: 33636308
pubmed: 33636308
pii: S0960-894X(21)00108-6
doi: 10.1016/j.bmcl.2021.127882
pii:
doi:

Substances chimiques

Cannabinoids 0
Receptor, Cannabinoid, CB1 0
Receptor, Cannabinoid, CB2 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

127882

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Published by Elsevier Ltd.

Auteurs

Thanh C Ho (TC)

Department of Chemistry, University of Hawaii at Manoa, 2545 The Mall, Honolulu, HI 96822, United States.

Marcus A Tius (MA)

Department of Chemistry, University of Hawaii at Manoa, 2545 The Mall, Honolulu, HI 96822, United States. Electronic address: tius@hawaii.edu.

Spyros P Nikas (SP)

Center for Drug Discovery, Department of Chemistry and Chemical Biology, and Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, United States.

Ngan K Tran (NK)

Center for Drug Discovery, Department of Chemistry and Chemical Biology, and Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, United States.

Fei Tong (F)

Center for Drug Discovery, Department of Chemistry and Chemical Biology, and Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, United States.

Han Zhou (H)

Center for Drug Discovery, Department of Chemistry and Chemical Biology, and Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, United States.

Nikolai Zvonok (N)

Center for Drug Discovery, Department of Chemistry and Chemical Biology, and Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, United States.

Alexandros Makriyannis (A)

Center for Drug Discovery, Department of Chemistry and Chemical Biology, and Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, United States. Electronic address: a.makriyannis@neu.edu.

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Classifications MeSH

questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Terpènes › Cannabinoïdes › Oxa-adamantyl cannabinoids.
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes toxicologiques › Relation dose-effet des médicaments › Oxa-adamantyl cannabinoids.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Oxa-adamantyl cannabinoids.
questionsmedicales.fr › Phénomènes chimiques › Structure moléculaire › Oxa-adamantyl cannabinoids.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs couplés aux protéines G › Récepteurs de cannabinoïdes › Récepteur cannabinoïde de type CB1 › Oxa-adamantyl cannabinoids.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs couplés aux protéines G › Récepteurs de cannabinoïdes › Récepteur cannabinoïde de type CB2 › Oxa-adamantyl cannabinoids.
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Relation structure-activité › Oxa-adamantyl cannabinoids.