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

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.

SUBMITTER: Engers DW

PROVIDER: S-EPMC2865690 | biostudies-other | 2009 Apr

REPOSITORIES: biostudies-other

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

Engers Darren W DW Rodriguez Alice L AL Williams Richard R Hammond Alexis S AS Venable Daryl D Oluwatola Oluwatomi O Sulikowski Gary A GA Conn P Jeffrey PJ Lindsley Craig W CW

ChemMedChem 20090401 4

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. ...[more]

PMID: 19197923

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