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)

  • J Med Chem. 2019 Feb 14;62(3):1690-1695. doi: 10.1021/acs.jmedchem.8b01810.
Carson W Reed ,  Samantha E Yohn ,  Jordan P Washecheck ,  Hanna F Roenfanz ,  Marc C Quitalig ,  Vincent B Luscombe ,  Matthew T Jenkins ,  Alice L Rodriguez ,  Darren W Engers ,  Anna L Blobaum ,  P Jeffrey Conn  1 ,  Colleen M Niswender  1 ,  Craig W Lindsley
Affiliations
  • 1. Vanderbilt Kennedy Center , Vanderbilt University School of Medicine , Nashville , Tennessee 37232 , United States.
PMID: 30608678 DOI: 10.1021/acs.jmedchem.8b01810
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.

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