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

作者：Stanley Nathan J; Hutchinson Mark R; Kvist Trine; Nielsen Birgitte; Mathiesen Jesper Mosolff; Brauner O**orne Hans; Avery Thomas D; Tiekink Edward R T; Pedersen Daniel Sejer; Irvine Rodney J; Abell Andrew D; Taylor Dennis K^*

来源：Bioorganic & Medicinal Chemistry, 2010, 18(16): 6089-6098.

DOI：10.1016/j.bmc.2010.06.051

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

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.

• 出版日期2010-8-15