Synthesis and SAR of a novel metabotropic glutamate receptor 4 (mGlu 4) antagonist: Unexpected 'molecular switch' from a closely related mGlu 4 positive allosteric modulator

Thomas Utley, Dustin Haddenham, James M. Salovich, Rocio Zamorano, Paige N. Vinson, Craig W. Lindsley, Corey R. Hopkins, Colleen M. Niswender

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Herein we report the discovery and SAR of a novel antagonist of metabotropic glutamate receptor 4 (mGlu 4). The antagonist was discovered via a molecular switch from a closely related mGlu 4 positive allosteric modulator (PAM). This antagonist (VU0448383) displays an IC 50 value of 8.2 ± 0.4 μM and inhibits an EC 80 glutamate response by 63.1 ± 6.6%.

Original languageEnglish (US)
Pages (from-to)6955-6959
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number23
DOIs
StatePublished - Dec 1 2011

Keywords

  • Antagonist
  • Metabotropic glutamate receptor 4
  • Molecular switch
  • mGlu

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Synthesis and SAR of a novel metabotropic glutamate receptor 4 (mGlu <sub>4</sub>) antagonist: Unexpected 'molecular switch' from a closely related mGlu <sub>4</sub> positive allosteric modulator'. Together they form a unique fingerprint.

  • Cite this