Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead

Richard Williams, C.M. Niswender, Q. Luo, U. Le, P.J. Conn, C.W. Lindsley

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

This Letter describes the synthesis and SAR of two mGluR4 positive allosteric modulator leads, 6 and 7. VU001171 (6) represents the most potent (EC50 = 650 nM), efficacious (141% Glu Max) and largest fold shift (36-fold) of any mGluR4 PAM reported to date. However, this work highlights the challenges in hit-to-lead for mGluR4 PAMs, with multiple confirmed HTS hits displaying little or no tractable SAR. (C) 2008 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)962-966
Number of pages5
JournalBioorganic & Medicinal Chemistry Letters
Volume19
Issue number3
DOIs
Publication statusPublished - 01 Feb 2009

ASJC Scopus subject areas

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

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