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
CW
Carson W
,
Yohn
SE
Samantha E
,
Washecheck
JP
Jordan P
,
Roenfanz
HF
Hanna F
,
Quitalig
MC
Marc C
,
Luscombe
VB
Vincent B
,
Jenkins
MT
Matthew T
,
Rodriguez
AL
Alice L
,
Engers
DW
Darren W
,
Blobaum
AL
Anna L
,
Conn
PJ
P Jeffrey
,
Niswender
CM
Colleen M
,
Lindsley
CW
Craig W
.
Journal of medicinal chemistry. 2019 1 17; 62(3).
1690-1695
Journal of medicinal chemistry. 2019 1 17; 62(3).
1690-1695
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