| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1369476 | Bioorganic & Medicinal Chemistry Letters | 2012 | 5 Pages |
Abstract
We report the optimization of a series of non-MPEP site metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulators (PAMs) based on a simple acyclic ether series. Modifications led to a gain of MPEP site interaction through incorporation of a chiral amide in conjunction with a nicotinamide core. A highly potent PAM, 8v (VU0404251), was shown to be efficacious in a rodent model of psychosis. These studies suggest that potent PAMs within topologically similar chemotypes can be developed to preferentially interact or not interact with the MPEP allosteric binding site.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Jason T. Manka, Paige N. Vinson, Karen J. Gregory, Ya Zhou, Richard Williams, Kiran Gogi, Emily Days, Satya Jadhav, Elizabeth J. Herman, Hilde Lavreysen, Claire Mackie, José M. Bartolomé, Gregor J. Macdonald, Thomas Steckler, J. Scott Daniels,