Alkyl indole-based cannabinoid type 2 receptor tools: Exploration of linker and fluorophore attachment

Alkyl indole-based cannabinoid type 2 receptor tools: Exploration of linker and fluorophore... Cannabinoid type 2 (CB2) receptor continues to emerge as a promising drug target for many diseases and conditions. New tools for studying CB2 receptor are required to further inform how this receptor functions in healthy and diseased states. The alkyl indole scaffold is a well-recognised ligand for cannabinoid receptors, and in this study the indole C5-7 positions were explored for linker and fluorophore attachment. A new high affinity, CB2 receptor selective inverse agonist was identified (16b) along with a general trend of C5-substituted indoles acting as agonists versus C7-substituted indoles acting as inverse agonists. The indole C7 position was found to be the most tolerant to linker extension and resulted in a high affinity inverse agonist with a medium length linker (19). Although a high affinity fluorescent ligand for CB2 receptor was not identified in this study, the indole C7 position shows great promise for fluorophore or probe attachment. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Medicinal Chemistry Elsevier

Alkyl indole-based cannabinoid type 2 receptor tools: Exploration of linker and fluorophore attachment

Alkyl indole-based cannabinoid type 2 receptor tools: Exploration of linker and fluorophore attachment

European Journal of Medicinal Chemistry 145 (2018) 770e789 Contents lists available at ScienceDirect European Journal of Medicinal Chemistry journal homepage: http://www.elsevier.com/locate/ejmech Research paper Alkyl indole-based cannabinoid type 2 receptor tools: Exploration of linker and fluorophore attachment a b b a a Anna G. Cooper , Christa MacDonald , Michelle Glass , Sarah Hook , Joel D.A. Tyndall , a, * Andrea J. Vernall School of Pharmacy, University of Otago, Dunedin, New Zealand Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand article i nf o abstract Article history: Cannabinoid type 2 (CB ) receptor continues to emerge as a promising drug target for many diseases and Received 23 September 2017 conditions. New tools for studying CB receptor are required to further inform how this receptor func- Received in revised form tions in healthy and diseased states. The alkyl indole scaffold is a well-recognised ligand for cannabinoid 23 November 2017 receptors, and in this study the indole C5-7 positions were explored for linker and fluorophore attach- Accepted 26 November 2017 ment. A new high affinity, CB receptor selective inverse agonist was identified (16b) along with a general Available online 28 November 2017 trend of C5-substituted indoles acting as agonists versus C7-substituted indoles acting as inverse ago- nists. The indole C7 position was found to be the most tolerant to linker extension and resulted in a high Keywords: affinity inverse agonist with a medium length linker (19). Although a high affinity fluorescent ligand for Cannabinoid type 2 receptor CB receptor was not identified in this study, the indole C7 position shows great promise for fluorophore Cannabinoid or probe attachment. Fluorescent probe Alkyl indole © 2017 Elsevier Masson SAS. All rights reserved. G protein-coupled receptor Abbreviations: BODIPY 630/650-X-OSu 6-(((4,4-difluoro-5-(2-thienyl)-4-bora-...
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Publisher
Elsevier
Copyright
Copyright © 2017 Elsevier Masson SAS
ISSN
0223-5234
eISSN
1768-3254
D.O.I.
10.1016/j.ejmech.2017.11.076
Publisher site
See Article on Publisher Site

Abstract

Cannabinoid type 2 (CB2) receptor continues to emerge as a promising drug target for many diseases and conditions. New tools for studying CB2 receptor are required to further inform how this receptor functions in healthy and diseased states. The alkyl indole scaffold is a well-recognised ligand for cannabinoid receptors, and in this study the indole C5-7 positions were explored for linker and fluorophore attachment. A new high affinity, CB2 receptor selective inverse agonist was identified (16b) along with a general trend of C5-substituted indoles acting as agonists versus C7-substituted indoles acting as inverse agonists. The indole C7 position was found to be the most tolerant to linker extension and resulted in a high affinity inverse agonist with a medium length linker (19). Although a high affinity fluorescent ligand for CB2 receptor was not identified in this study, the indole C7 position shows great promise for fluorophore or probe attachment.

Journal

European Journal of Medicinal ChemistryElsevier

Published: Feb 10, 2018

References

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