2. Academic Validation
  3. VU6010608, a Novel mGlu7 NAM from a Series of N-(2-(1 H-1,2,4-Triazol-1-yl)-5-(trifluoromethoxy)phenyl)benzamides

VU6010608, a Novel mGlu7 NAM from a Series of N-(2-(1 H-1,2,4-Triazol-1-yl)-5-(trifluoromethoxy)phenyl)benzamides

  • ACS Med Chem Lett. 2017 Nov 8;8(12):1326-1330. doi: 10.1021/acsmedchemlett.7b00429.
Carson W Reed 1,  Kevin M McGowan 1,  Paul K Spearing 1,  Branden J Stansley 1,  Hanna F Roenfanz 1,  Darren W Engers 1,  Alice L Rodriguez 1,  Eileen M Engelberg 1,  Vincent B Luscombe 1,  Matthew T Loch 1,  Daniel H Remke 1,  Jerri M Rook 1,  Anna L Blobaum 1,  P Jeffrey Conn 1 2,  Colleen M Niswender 1 2,  Craig W Lindsley 1 1
Affiliations

Affiliations

  • 1 Vanderbilt Center for Neuroscience Drug Discovery, Department of Pharmacology, and Department of Biochemistry and Chemistry, Vanderbilt University, Nashville, Tennessee 37232, United States.
  • 2 Vanderbilt Kennedy Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.
PMID: 29259756 DOI: 10.1021/acsmedchemlett.7b00429
Abstract

Herein, we report the structure-activity relationships within a series of mGlu7 NAMs based on an N-(2-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl)benzamide core with excellent CNS penetration (Kp 1.9-5.8 and Kp,uu 0.4-1.4). Analogues in this series displayed steep SAR. Of these, VU6010608 (11a) emerged with robust efficacy in blocking high frequency stimulated long-term potentiation in electrophysiology studies.

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