An orally bioavailable positive allosteric modulator of the mGlu4 receptor with efficacy in an animal model of motor dysfunction.

Abstract

A high-throughput screening campaign identified 4-((E)-styryl)-pyrimidin-2-ylamine (11) as a positive allosteric modulator of the metabotropic glutamate (mGlu) receptor subtype 4. An evaluation of the structure-activity relationships (SAR) of 11 is described and the efficacy of this compound in a haloperidol-induced catalepsy rat model following oral administration is presented.

• Authors: Stephen P East, Samantha Bamford, Matthias G A Dietz, Christian Eickmeier, Adam Flegg, Boris Ferger, Mark J Gemkow, Ralf Heilker, Bastian Hengerer, Adrian Kotey, Pui Loke, Gerhard Schänzle, Hans-Dieter Schubert, John Scott, Mark Whittaker, Mildred Williams, Przemyslaw Zawadzki, Kai Gerlach
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 20 Issue 16 Pg. 4901-5 (Aug 15 2010) ISSN: 1464-3405 [Electronic] England
• PMID: 20638279 (Publication Type: Journal Article)
• Copyright: 2010 Elsevier Ltd. All rights reserved.

Chemical References

• 4-styrylpyrimidin-2-ylamine
• Pyrimidines
• Receptors, Metabotropic Glutamate
• Styrenes
• metabotropic glutamate receptor 4

Topics

• Administration, Oral
• Allosteric Regulation
• Animals
• Catalepsy (chemically induced, drug therapy)
• High-Throughput Screening Assays
• Humans
• Models, Animal
• Motor Activity (physiology)
• Pyrimidines (chemical synthesis, chemistry, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Receptors, Metabotropic Glutamate (chemistry, metabolism)
• Structure-Activity Relationship
• Styrenes (chemical synthesis, chemistry, therapeutic use)