Abstract
Development of SAR in an aryl ether series of mGlu5 NAMs leading to the identification of tool compound VU0409106 is described in this Letter. VU0409106 is a potent and selective negative allosteric modulator of mGlu 5 that binds at the known allosteric binding site and demonstrates good CNS exposure following intraperitoneal dosing in mice. VU0409106 also proved efficacious in a mouse marble burying model of anxiety, an assay known to be sensitive to mGlu5 antagonists as well as clinically efficacious anxiolytics.
Original language | English |
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Pages (from-to) | 5779-5785 |
Number of pages | 7 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 23 |
Issue number | 21 |
DOIs | |
State | Published - 1 Nov 2013 |
Keywords
- Allosteric modulator
- Anxiety
- CNS
- Glutamate
- mGlu