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

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.

SUBMITTER: Reed CW

PROVIDER: S-EPMC5733308 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Reed Carson W CW McGowan Kevin M KM Spearing Paul K PK Stansley Branden J BJ Roenfanz Hanna F HF Engers Darren W DW Rodriguez Alice L AL Engelberg Eileen M EM Luscombe Vincent B VB Loch Matthew T MT Remke Daniel H DH Rook Jerri M JM Blobaum Anna L AL Conn P Jeffrey PJ Niswender Colleen M CM Lindsley Craig W CW

ACS medicinal chemistry letters 20171108 12

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. ...[more]

PMID: 29259756

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