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

14 Citations (Scopus)

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

Fingerprint

Excitatory Amino Acid Antagonists
Modulators
Switches
Glutamic Acid
metabotropic glutamate receptor 4
VU0448383

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

Cite this

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

In: Bioorganic and Medicinal Chemistry Letters, Vol. 21, No. 23, 01.12.2011, p. 6955-6959.

Research output: Contribution to journalArticle

Utley, Thomas ; Haddenham, Dustin ; Salovich, James M. ; Zamorano, Rocio ; Vinson, Paige N. ; Lindsley, Craig W. ; Hopkins, Corey R. ; Niswender, Colleen M. / 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. In: Bioorganic and Medicinal Chemistry Letters. 2011 ; Vol. 21, No. 23. pp. 6955-6959.
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