Development of selective, fluorescent cannabinoid type 2 receptor ligands based on a 1,8-naphthyridin-2-(1H)-one-3-carboxamide scaffold

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dc.contributor.author Cooper, AG en
dc.contributor.author Oyagawa, Caitlin en
dc.contributor.author Manning, JJ en
dc.contributor.author Singh, S en
dc.contributor.author Hook, S en
dc.contributor.author Grimsey, Natasha en
dc.contributor.author Glass, Michelle en
dc.contributor.author Tyndall, JDA en
dc.contributor.author Vernall, AJ en
dc.date.accessioned 2019-03-11T20:36:22Z en
dc.date.available 2018-10-18 en
dc.date.issued 2018-10-23 en
dc.identifier.issn 2040-2503 en
dc.identifier.uri http://hdl.handle.net/2292/45906 en
dc.description.abstract Cannabinoid type 2 (CB2) receptor has been implicated in several diseases and conditions, however no CB2 receptor selective drugs have made it to market. The aim of this study was to develop fluorescent ligands as CB2 receptor tools, to enable an increased understanding of CB2 receptor expression and signalling and thereby accelerate drug discovery. Fluorescent ligands have been successfully developed for other receptors, however none with adequate subtype selectivity or imaging properties have been reported for CB2 receptor. A series of 1,8-naphthyridin-2-(1H)-one-3-carboxamides with linkers and fluorophores appended in the N1 and C3-positions were developed. Molecular modelling indicated the C3 cis-cyclohexanol-linked compounds directed the linker out of the CB2 receptor between transmembrane helices 1 and 7. Herein we report fluorescent ligand 32 (hCB2 pKi = 6.33 ± 0.02) as one of the highest affinity, selective CB2 receptor fluorescent ligands reported. Despite 32 displaying poor specific labelling of CB2 receptor, the naphthyridine scaffold with this linker remains highly promising for future development of CB2 receptor tools. en
dc.relation.ispartofseries MedChemComm en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Development of selective, fluorescent cannabinoid type 2 receptor ligands based on a 1,8-naphthyridin-2-(1H)-one-3-carboxamide scaffold en
dc.type Journal Article en
dc.identifier.doi 10.1039/C8MD00448J en
dc.rights.holder Copyright: The author en
pubs.author-url https://doi.org/10.1039/C8MD00448J en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Article en
pubs.elements-id 756102 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Pharmacology en
dc.identifier.eissn 2040-2511 en
pubs.record-created-at-source-date 2018-11-11 en
pubs.online-publication-date 2018-10-23 en
pubs.dimensions-id 30647881 en


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