Discovery of an Orally Bioavailable and Central Nervous System (CNS) Penetrant mGlu Negative Allosteric Modulator (NAM) in Vivo Tool Compound: N-(2-(1 H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl)-4-(cyclopropylmethoxy)-3-methoxybenzamide (VU6012962)
AUTHORS
Reed
CWCarson W ,
Yohn
SESamantha E ,
Washecheck
JPJordan P ,
Roenfanz
HFHanna F ,
Quitalig
MCMarc C ,
Luscombe
VBVincent B ,
Jenkins
MTMatthew T ,
Rodriguez
ALAlice L ,
Engers
DWDarren W ,
Blobaum
ALAnna L ,
Conn
PJP Jeffrey ,
Niswender
CMColleen M ,
Lindsley
CWCraig W .
Journal of medicinal chemistry. 2019 1 17; 62(3).
1690-1695
- PMID: 30608678[PubMed].
ABSTRACT
Herein, we report the discovery of a new, orally bioavailable and CNS-penetrant metabotropic glutamate receptor 7 (mGlu) negative allosteric modulator (NAM) that achieves exposure in cerebral spinal fluid (CSF) 2.5× above the in vitro IC at minimum effective doses (MEDs) of 3 mg/kg in preclinical anxiety models.
Tags: 2019