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ID: ALA4665820

Journal: ACS Med Chem Lett

Title: Discovery of VU6027459: A First-in-Class Selective and CNS Penetrant mGlu Positive Allosteric Modulator Tool Compound.

Authors: Reed CW,Kalbfleisch JJ,Wong MJ,Washecheck JP,Hunter A,Rodriguez AL,Blobaum AL,Conn PJ,Niswender CM,Lindsley CW

Abstract: Herein, we report the discovery of the first selective and CNS penetrant mGlu PAM (VU6027459) derived from a "molecular switch" within a selective mGlu NAM chemotype. VU6027459 displayed CNS penetration in both mice (K = 2.74) and rats (K= 4.78), it was orally bioavailable in rats (%F = 69.5), and undesired activity at DAT was ablated.

CiteXplore: 32944146

DOI: 10.1021/acsmedchemlett.0c00432