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

Authors

N.J. Stanley
M.R. Hutchinson
T. Kvist
B. Nielsen
J.M. Mathiesen
H. Brauner-Osborne
T.D. Avery
E.R.T. Tiekink
D.S. Pedersen
R. Irvine
A.D. Abell
D.K. Taylor

Document Type

Article

Publication Date

1-1-2010

Abstract

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. (C) 2010 Elsevier Ltd. All rights reserved.

Keywords

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

Publication Title

Bioorganic & Medicinal Chemistry

Volume

18

Issue

16

Publisher

Elsevier

Publisher Location

THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND