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

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

doi:10.1016/j.bmc.2010.06.051

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

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

4 Citations (Scopus)

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.

Original language	English
Journal	Bioorganic & Medicinal Chemistry
Volume	18
Issue number	16
Pages (from-to)	6089-6098
ISSN	0968-0896
DOIs	https://doi.org/10.1016/j.bmc.2010.06.051
Publication status	Published - 15 Aug 2010

Keywords

Former Faculty of Pharmaceutical Sciences

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10.1016/j.bmc.2010.06.051

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Stanley, N. J., Hutchinson, M. R., Kvist, T., Nielsen, B., Mathiesen, J. M., Bräuner-Osborne, H., Avery, T. D., Tiekink, E. R. T., Pedersen, D. S., Irvine, R. J., Abell, A. D., & Taylor, D. K. (2010). A new metabotropic glutamate receptor agonist with in vivo anti-allodynic activity. Bioorganic & Medicinal Chemistry, 18(16), 6089-6098. https://doi.org/10.1016/j.bmc.2010.06.051

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title = "A new metabotropic glutamate receptor agonist with in vivo anti-allodynic activity",

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.",

keywords = "Former Faculty of Pharmaceutical Sciences",

author = "Stanley, {Nathan J} and Hutchinson, {Mark R} and Trine Kvist and Birgitte Nielsen and Mathiesen, {Jesper M} and Hans Br{\"a}uner-Osborne and Avery, {Thomas D} and Tiekink, {Edward R T} and Pedersen, {Daniel Sejer} and Irvine, {Rodney J} and Abell, {Andrew D} and Taylor, {Dennis K}",

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

year = "2010",

month = aug,

day = "15",

doi = "10.1016/j.bmc.2010.06.051",

language = "English",

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pages = "6089--6098",

journal = "Bioorganic & Medicinal Chemistry",

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TY - JOUR

T1 - A new metabotropic glutamate receptor agonist with in vivo anti-allodynic activity

AU - Stanley, Nathan J

AU - Hutchinson, Mark R

AU - Kvist, Trine

AU - Nielsen, Birgitte

AU - Mathiesen, Jesper M

AU - Bräuner-Osborne, Hans

AU - Avery, Thomas D

AU - Tiekink, Edward R T

AU - Pedersen, Daniel Sejer

AU - Irvine, Rodney J

AU - Abell, Andrew D

AU - Taylor, Dennis K

N1 - Keywords: 1,2-Dioxines; Carboxycyclopropylglycines; Metabotropic glutamate receptors; In vivo; Neuropathic pain; Allodynia

PY - 2010/8/15

Y1 - 2010/8/15

N2 - 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.

AB - 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.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1016/j.bmc.2010.06.051

DO - 10.1016/j.bmc.2010.06.051

M3 - Journal article

C2 - 20638290

SN - 0968-0896

VL - 18

SP - 6089

EP - 6098

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 16

ER -

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

Abstract

Keywords

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