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
  • 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.
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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