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Synthesis, SAR and Unanticipated Pharmacological Profiles of Analogues of the mGluR5 Ago‐potentiator ADX‐47273
Author(s) -
Engers Darren W.,
Rodriguez Alice L.,
Williams Richard,
Hammond Alexis S.,
Venable Daryl,
Oluwatola Oluwatomi,
Sulikowski Gary A.,
Conn P. Jeffrey,
Lindsley Craig W.
Publication year - 2009
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200800357
Subject(s) - potentiator , metabotropic glutamate receptor 5 , allosteric regulation , long term potentiation , chemistry , stereochemistry , glutamate receptor , metabotropic glutamate receptor , pharmacology , medicine , biochemistry , receptor
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.