901390-17-8Relevant articles and documents
Discovery of VU0431316: A negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety
Bates, Brittney S.,Rodriguez, Alice L.,Felts, Andrew S.,Morrison, Ryan D.,Venable, Daryl F.,Blobaum, Anna L.,Byers, Frank W.,Lawson, Kera P.,Daniels, J. Scott,Niswender, Colleen M.,Jones, Carrie K.,Conn, P. Jeffrey,Lindsley, Craig W.,Emmitte, Kyle A.
, p. 3307 - 3314 (2014)
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.
