Scottish Ophthalmic Imaging Society meeting Feb 14, 2020 09:30 AM - 05:00 PM — Royal Society of Edinburgh, 22-26 George Street, Edinburgh
8th Annual Scottish Radiotherapy Research Forum Mar 12, 2020 10:00 AM - 04:30 PM — Stirling Court Hotel, University of Stirling
Medical Imaging Convention 2020 Mar 17, 2020 10:00 PM - 04:00 PM — National Exhibition Centre, Birmingham, England
9th SINAPSE Neuro-oncology Imaging Meeting Mar 19, 2020 12:00 AM — West Park Conferencing & Events, 319 Perth Road, Dundee DD2 1NN

Synthesis and biological evaluation of (-)-kainic acid analogues as phospholipase D-coupled metabotropic glutamate receptor ligands

Author(s): C. Zanato, S. Watson, G. S. Bewick, W. T. Harrison, M. Zanda

Abstract:
(-)-Kainic acid potently increases stretch-induced afferent firing in muscle spindles, probably acting through a hitherto uncloned phospholipase D (PLD)-coupled mGlu receptor. Structural modification of (-)-kainic acid was undertaken to explore the C-4 substituent effect on the pharmacology related to muscle spindle firing. Three analogues 1a-c were synthesised by highly stereoselective additions of a CF3, a hydride and an alkynyl group to the Re face of the key pyrrolidin-4-one intermediate 5a followed by further structural modifications. Only the 4-(1,2,3-triazolyl)-kainate derivative 1c retained the kainate-like agonism, increasing firing in a dose-dependent manner. Further modification of 1c by introduction of a PEG-biotin chain on the 1,2,3-triazole fragment afforded compound 14 which retained robust agonism at 1 muM and appears to be suitable for future use in pull-down assays and far western blotting for PLD-mGluR isolation.

Full version: Available here

Click the link to go to an external website with the full version of the paper


ISBN: 1477-0539 (Electronic) 1477-0520 (Linking)
Publication Year: 2014
Periodical: Org Biomol Chem
Periodical Number: 47
Volume: 12
Pages: 9638-43
Author Address: Kosterlitz Centre for Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, AB25 2ZD, Scotland, UK. m.zanda@abdn.ac.uk.