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Journal articles
Synthesis and biological evaluation of 1-amino-2-phosphonomethylcyclopropanecarboxylic acids, new group III metabotropic glutamate receptor agonists.
Pauline Sibille
1
Sébastien Lopez
2
Isabelle Brabet
3
Ornella Valenti
4
Nadia Oueslati
3
Florence Gaven
3
Cyril Goudet
3
Hugues-Olivier Bertrand
5
Jacques Neyton
6
Michael Marino
4
Marianne Amalric
2
Jean-Philippe Pin
3
Francine Acher
1, *
*
Corresponding author
5
Accelrys
Nadia Oueslati 3
Author
Florence Gaven 3
Author
Cyril Goudet 3
Author IdHAL : cyril-goudet ResearcherId : http://www.researcherid.com/rid/AAE-3415-2020 IdRef : https://www.idref.fr/162209274 ORCID : https://orcid.org/0000-0002-8255-3535
Hugues-Olivier Bertrand 5
Author
Jacques Neyton 6
Author
Michael J. Marino 4
Author
Marianne Amalric 2
Author IdHAL : marianne-amalric
Jean-Philippe Pin 3
Author IdHAL : jean-philippe-pin ORCID : https://orcid.org/0000-0002-1423-345X
Francine C. Acher 1
Correspondent author
1
LCBPT - UMR 8601 - Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (45 Rue des Saints-Pères
75270 PARIS CEDEX 06 - France)
- UPD5 - Université Paris Descartes - Paris 5 : UMR 8601 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR 8601 (France)
2
LNC - Laboratoire de Neurosciences Cognitives [Marseille] (Pole 3 C Case C 3 Place Victor Hugo 13331 Marseille Cedex 3 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR7291 (France)
- AMU - Aix Marseille Université : UMR7291 (Aix-Marseille Université Jardins du Pharo 58 Boulevard Charles Livon 13284 Marseille cedex 7 - France)
3
IGF - Institut de Génomique Fonctionnelle (141, Rue de la Cardonille 34094 Montpellier cedex 5 - France)
- UM - Université de Montpellier (163 rue Auguste Broussonnet - 34090 Montpellier - France)
- UM1 - Université Montpellier 1 (5, boulevard Henri IV - CS 19044 - 34967 Montpellier cedex - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1191 (101, rue de Tolbiac, 75013 Paris - France)
- UM2 - Université Montpellier 2 - Sciences et Techniques (Place Eugène Bataillon - 34095 Montpellier cedex 5 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR5203 (France)
4
Department of Molecular Neurology (Merck Research Laboratories, West Point, Pennsylvania - United States)
- Merck Research Laboratories (United States)
6
NEURO - Laboratoire de Neurobiologie (UMR 8544) (46 Rue d'Ulm 75230 PARIS CEDEX 05 - France)
- ENS Paris - École normale supérieure - Paris (45, Rue d'Ulm - 75230 Paris cedex 05 - France)
- PSL - Université Paris sciences et lettres (60 rue Mazarine 75006 Paris - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR8544 (France)
Abstract : Stereoisomers of 1-amino-2-phosphonomethylcyclopropanecarboxylic acid (APCPr), conformationally restricted analogues of L-AP4 (2-amino-4-phosphonobutyric acid), have been prepared and evaluated at recombinant group III metabotropic glutamate receptors. They activate these receptors over a broad range of potencies. The most potent isomer (1S,2R)-APCPr displays a similar pharmacological profile as that of L-AP4 (EC50 0.72, 1.95, >500, 0.34 microM at mGlu4, 6, 7, 8 receptors, respectively, and no effect at group I/II mGluRs). It was characterized on native receptors located in the basal ganglia (BG) where it induced a robust and reversible inhibition of synaptic transmission. It was tested in vivo in haloperidol-induced catalepsy, a model of Parkinsonian akinesia, by direct infusion in the globus pallidus of the BG. At a dose of 0.5 nmol/microL, catalepsy was significantly antagonized. This study reveals that (1S,2R)-APCPr is a potent group III mGluR agonist and confirms that these receptors may be considered as a therapeutic target in the Parkinson's disease.
Document type :
Journal articles
Complete list of metadatas
https://www.hal.inserm.fr/inserm-00318976
Contributor : Cyril Goudet <>
Submitted on : Friday, September 5, 2008 - 5:11:37 PM
Last modification on : Monday, December 21, 2020 - 2:26:08 PM
Long-term archiving on: : Saturday, November 26, 2016 - 1:19:49 AM
Contributor : Cyril Goudet <>
Submitted on : Friday, September 5, 2008 - 5:11:37 PM
Last modification on : Monday, December 21, 2020 - 2:26:08 PM
Long-term archiving on: : Saturday, November 26, 2016 - 1:19:49 AM
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Identifiers
- HAL Id : inserm-00318976, version 1
- DOI : 10.1021/jm070262c
- PUBMED : 17602546
Collections
INSERM | CNRS | UNIV-PARIS5 | ENS-PARIS | UNIV-AMU | USPC | LNC | BS | UNIV-MONTPELLIER | UNIV-PARIS | UP-SCIENCES | PSL
Citation
Pauline Sibille, Sébastien Lopez, Isabelle Brabet, Ornella Valenti, Nadia Oueslati, et al.. Synthesis and biological evaluation of 1-amino-2-phosphonomethylcyclopropanecarboxylic acids, new group III metabotropic glutamate receptor agonists.. Journal of Medicinal Chemistry, American Chemical Society, 2007, 50 (15), pp.3585-95. ⟨10.1021/jm070262c⟩. ⟨inserm-00318976⟩
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