Stanley, N.Hutchinson, M.Kvist, T.Nielsen, B.Mathiesen, J.Brauner-Osborne, H.Avery, T.Tiekink, E.Pedersen, D.Irvine, R.Abell, A.Taylor, D.2010-11-122010-11-122010Bioorganic and Medicinal Chemistry, 2010; 18(16):6089-60980968-08961464-3391http://hdl.handle.net/2440/61716As 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.en© 2010 Elsevier Ltd. All rights reservedCHO CellsAnimalsCricetulusRatsRats, Sprague-DawleyNeuralgiaHyperalgesiaCyclopropanesGlycineReceptors, Metabotropic GlutamateAnalgesicsCricetinaeMaleJournal article002010037510.1016/j.bmc.2010.06.0510002806641000332-s2.0-7795547258833594Stanley, N. [0000-0002-2625-9876]Hutchinson, M. [0000-0003-2154-5950]Avery, T. [0000-0001-6882-5461]Abell, A. [0000-0002-0604-2629]Taylor, D. [0000-0002-3302-4610] [0000-0002-4274-3983] [0000-0003-0633-7424]