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ID: ALA4138139
Journal: ACS Med Chem Lett
Title: Discovery of VU6005649, a CNS Penetrant mGlu7/8 Receptor PAM Derived from a Series of Pyrazolo[1,5-a]pyrimidines.
Authors: Abe M, Seto M, Gogliotti RG, Loch MT, Bollinger KA, Chang S, Engelberg EM, Luscombe VB, Harp JM, Bubser M, Engers DW, Jones CK, Rodriguez AL, Blobaum AL, Conn PJ, Niswender CM, Lindsley CW.
Abstract: Herein, we report the structure-activity relationships within a series of mGlu7 PAMs based on a pyrazolo[1,5-a]pyrimidine core with excellent CNS penetration (Kps > 1 and Kp,uus > 1). Analogues in this series proved to display a range of Group III mGlu receptor selectivity, but VU6005649 emerged as the first dual mGlu7/8 PAM, filling a void in the Group III mGlu receptor PAM toolbox and demonstrating in vivo efficacy in a mouse contextual fear conditioning model.
CiteXplore: 29057060