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 mGlu 5 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 mGlu 5 antagonists and other anxiolytics, produced dose proportional effects.
Original language | English |
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Pages (from-to) | 3307-3314 |
Number of pages | 8 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 24 |
Issue number | 15 |
DOIs | |
State | Published - 1 Aug 2014 |
Keywords
- Allosteric modulator
- Anxiety
- CNS
- Glutamate