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

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

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 (K p 1.9–5.8 and K p,uu 0.4–1.4). Analogues in this series displayed steep SAR. Of these, VU6010608...

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Veröffentlicht in:ACS medicinal chemistry letters 2017-12, Vol.8 (12), p.1326-1330
Hauptverfasser: Reed, Carson W, McGowan, Kevin M, Spearing, Paul K, Stansley, Branden J, Roenfanz, Hanna F, Engers, Darren W, Rodriguez, Alice L, Engelberg, Eileen M, Luscombe, Vincent B, Loch, Matthew T, Remke, Daniel H, Rook, Jerri M, Blobaum, Anna L, Conn, P. Jeffrey, Niswender, Colleen M, Lindsley, Craig W
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Sprache:eng
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Zusammenfassung: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 (K p 1.9–5.8 and K p,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.
ISSN:1948-5875
1948-5875
DOI:10.1021/acsmedchemlett.7b00429