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
Vanderbilt Center for Neuroscience Drug Discovery, Department of Pharmacology, and Department of Biochemistry and Chemistry, Vanderbilt University, Nashville, Tennessee 37232, United States.
Vanderbilt Kennedy Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.
ACS Med Chem Lett. 2017 Nov 8;8(12):1326-1330. doi: 10.1021/acsmedchemlett.7b00429. eCollection 2017 Dec 14.
Herein, we report the structure-activity relationships within a series of mGlu NAMs based on an -(2-(1-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl)benzamide core with excellent CNS penetration ( 1.9-5.8 and 0.4-1.4). Analogues in this series displayed steep SAR. Of these, VU6010608 () emerged with robust efficacy in blocking high frequency stimulated long-term potentiation in electrophysiology studies.
在此，我们报告了一系列基于-(2-(1-1,2,4-三唑-1-基)-5-(三氟甲氧基)苯基)苯甲酰胺核心且具有出色中枢神经系统渗透性(1.9 - 5.8和0.4 - 1.4)的代谢型谷氨酸负变构调节剂(mGlu NAMs)的构效关系。该系列类似物呈现出明显的构效关系。其中，VU6010608( )在电生理研究中表现出强大的阻断高频刺激诱导的长时程增强的功效。
