Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu1 |
| |
Authors: | 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 |
| |
Affiliation: | 1. Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA;2. Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA;3. Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA |
| |
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: | Glutamate GPCR Allosteric modulator CNS |
本文献已被 ScienceDirect 等数据库收录! |
|