| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 10591040 | Bioorganic & Medicinal Chemistry Letters | 2014 | 8 Pages |
Abstract
Development of SAR in an aryl ether series of mGlu5 NAMs leading to the identification of pyrazine analog VU0431316 is described in this Letter. VU0431316 is a potent and selective non-competitive antagonist of mGlu5 that binds at a known allosteric binding site. VU0431316 demonstrates an attractive DMPK profile, including moderate clearance and good bioavailability in rats. Intraperitoneal (IP) dosing of VU0431316 in a mouse marble burying model of anxiety, an assay known to be sensitive to mGlu5 antagonists and other anxiolytics, produced dose proportional effects.
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Authors
Brittney S. Bates, Alice L. Rodriguez, Andrew S. Felts, Ryan D. Morrison, Daryl F. Venable, Anna L. Blobaum, Frank W. Byers, Kera P. Lawson, J. Scott Daniels, Colleen M. Niswender, Carrie K. Jones, P. Jeffrey Conn, Craig W. Lindsley, Kyle A. Emmitte,