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

Authors: East SP, Bamford S, Dietz MG, Eickmeier C, Flegg A, Ferger B, Gemkow MJ, Heilker R, Hengerer B, Kotey A, Loke P, Schänzle G, Schubert HD, Scott J, Whittaker M, Williams M, Zawadzki P, Gerlach K.
Publisher/Year: Bioorg Med Chem Lett. 2010 Aug 15;20(16):4901-5. Epub 2010 Jun 25.
Pub Med ID/Journal ID: PMID:20638279


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. 2010 Elsevier Ltd. All rights reserved.