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 |
|---|---|
| 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 |
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Keywords
- Allosteric modulator
- Anxiety
- CNS
- Glutamate
- mGlu
Cite this
}
Discovery of VU0409106 : A negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety. / Felts, Andrew S.; Rodriguez, Alice L.; Morrison, Ryan D.; Venable, Daryl F.; Manka, Jason T.; Bates, Brittney S.; Blobaum, Anna L.; Byers, Frank W.; Daniels, J. Scott; Niswender, Colleen M.; Jones, Carrie K.; Conn, P. Jeffrey; Lindsley, Craig W.; Emmitte, Kyle A.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 21, 01.11.2013, p. 5779-5785.Research output: Contribution to journal › Article
TY - JOUR
T1 - Discovery of VU0409106
T2 - A negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety
AU - Felts, Andrew S.
AU - Rodriguez, Alice L.
AU - Morrison, Ryan D.
AU - Venable, Daryl F.
AU - Manka, Jason T.
AU - Bates, Brittney S.
AU - Blobaum, Anna L.
AU - Byers, Frank W.
AU - Daniels, J. Scott
AU - Niswender, Colleen M.
AU - Jones, Carrie K.
AU - Conn, P. Jeffrey
AU - Lindsley, Craig W.
AU - Emmitte, Kyle A.
PY - 2013/11/1
Y1 - 2013/11/1
N2 - 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.
AB - 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.
KW - Allosteric modulator
KW - Anxiety
KW - CNS
KW - Glutamate
KW - mGlu
UR - http://www.scopus.com/inward/record.url?scp=84885187910&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2013.09.001
DO - 10.1016/j.bmcl.2013.09.001
M3 - Article
C2 - 24074843
AN - SCOPUS:84885187910
VL - 23
SP - 5779
EP - 5785
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 21
ER -