Discovery of an Orally Bioavailable and Central Nervous System (CNS) Penetrant mGlu₇ Negative Allosteric Modulator (NAM) in Vivo Tool Compo...

Basic Information

ID: ALA4422629

Journal: J Med Chem

Title: Discovery of an Orally Bioavailable and Central Nervous System (CNS) Penetrant mGlu₇ 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, Yohn SE, Washecheck JP, Roenfanz HF, Quitalig MC, Luscombe VB, Jenkins MT, Rodriguez AL, Engers DW, Blobaum AL, Conn PJ, Niswender CM, Lindsley CW.

Abstract: Herein, we report the discovery of a new, orally bioavailable and CNS-penetrant metabotropic glutamate receptor 7 (mGlu₇) negative allosteric modulator (NAM) that achieves exposure in cerebral spinal fluid (CSF) 2.5× above the in vitro IC₅₀ at minimum effective doses (MEDs) of 3 mg/kg in preclinical anxiety models.

CiteXplore: 30608678

DOI: 10.1021/acs.jmedchem.8b01810

Patent ID: ┄