2. Academic Validation
  3. Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu1

Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu1

  • Bioorg Med Chem Lett. 2013 Sep 15;23(18):5091-6. doi: 10.1016/j.bmcl.2013.07.029.
Jason T Manka 1,  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
Affiliations

Affiliation

  • 1 Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
PMID: 23932792 DOI: 10.1016/j.bmcl.2013.07.029
Abstract

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.

Keywords

Allosteric modulator; CNS; GPCR; Glutamate; Octahydropyrrolo[3,4-c]pyrrole; mGlu(1).

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