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


AUTHORS

Manka JTJason T , Rodriguez ALAlice L , Morrison RDRyan D , Venable DFDaryl F , Cho HPHyekyung P , Blobaum ALAnna L , Daniels JSJ Scott , Niswender CMColleen M , Conn PJP Jeffrey , Lindsley CWCraig W , Emmitte KAKyle A . Bioorganic & medicinal chemistry letters. 2013 7 23; 23(18). 5091-6

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.



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