A new metabotropic glutamate receptor agonist with in vivo anti-allodynic activity

Research output: Contribution to journalJournal articleResearchpeer-review

Nathan J Stanley, Mark R Hutchinson, Trine Kvist, Birgitte Nielsen, Jesper M Mathiesen, Hans Bräuner-Osborne, Thomas D Avery, Edward R T Tiekink, Daniel Sejer Pedersen, Rodney J Irvine, Andrew D Abell, Dennis K Taylor

As part of the vital search towards improved therapeutic agents for the treatment of neuropathic pain, the central nervous system glutamate receptors have become a major focus of research. Outlined herein are the syntheses of two new biologically active 3'-cycloalkyl-substituted carboxycyclopropylglycines, utilizing novel synthetic chemistry. The reaction between substituted 1,2-dioxines and an aminophosphonate furnished the cyclopropane core in a single step with all required stereochemistry of pendant groups. In vitro binding assays at metabotropic glutamate receptors revealed selective activity. In vivo testing in a rodent model of neuropathic pain indicated one amino acid significantly and dose-dependently decreased mechanical allodynia.
Original languageEnglish
JournalBioorganic & Medicinal Chemistry
Volume18
Issue number16
Pages (from-to)6089-6098
ISSN0968-0896
DOIs
Publication statusPublished - 2010

Bibliographical note

Keywords: 1,2-Dioxines; Carboxycyclopropylglycines; Metabotropic glutamate receptors; In vivo; Neuropathic pain; Allodynia

ID: 21361781