2. Academic Validation
  3. Synthesis, SAR and unanticipated pharmacological profiles of analogues of the mGluR5 ago-potentiator ADX-47273

Synthesis, SAR and unanticipated pharmacological profiles of analogues of the mGluR5 ago-potentiator ADX-47273

  • ChemMedChem. 2009 Apr;4(4):505-11. doi: 10.1002/cmdc.200800357.
Darren W Engers 1,  Alice L Rodriguez,  Richard Williams,  Alexis S Hammond,  Daryl Venable,  Oluwatomi Oluwatola,  Gary A Sulikowski,  P Jeffrey Conn,  Craig W Lindsley
Affiliations

Affiliation

  • 1 Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232-6600, USA.
PMID: 19197923 DOI: 10.1002/cmdc.200800357
Abstract

An iterative analogue library synthesis strategy rapidly developed comprehensive SAR for the mGluR5 ago-potentiator ADX-47273. This effort identified key substituents in the 3-position of oxadiazole that engendered either mGluR5 ago-potentiation or pure mGluR5 positive allosteric modulation. The mGluR5 positive allosteric modulators identified possessed the largest fold shifts (up to 27.9-fold) of the glutamate CRC reported to date as well as providing improved physiochemical properties.

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