Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu 1

Jason T. Manka, Alice L. Rodriguez, Ryan D. Morrison, Daryl F. Venable, Hyekyung P. Cho, Anna L. Blobaum, J. Scott Daniels, Colleen M. Niswender, P. Jeffrey Conn, Craig W. Lindsley, Kyle A. Emmitte

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10 Scopus citations


Development of SAR in an octahydropyrrolo[3,4-c]pyrrole series of negative allosteric modulators of mGlu1 using a functional cell-based assay is described in this Letter. The octahydropyrrolo[3,4-c]pyrrole scaffold was chosen as an isosteric replacement for the piperazine ring found in the initial hit compound. Characterization of selected compounds in protein binding assays was used to identify the most promising analogs, which were then profiled in P450 inhibition assays in order to further assess the potential for drug-likeness within this series of compounds.

Original languageEnglish
Pages (from-to)5091-5096
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Issue number18
StatePublished - 15 Sep 2013


  • Allosteric modulator
  • CNS
  • GPCR mGlu
  • Glutamate
  • Octahydropyrrolo[3,4-c]pyrrole


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