Discovery of VU6027459: A First-in-Class Selective and CNS Penetrant mGlu7 Positive Allosteric Modulator Tool Compound

Discovery of VU6027459: A First-in-Class Selective and CNS Penetrant mGlu7 Positive Allosteric Modulator Tool Compound

Herein, we report the discovery of the first selective and CNS penetrant mGlu7 PAM (VU6027459) derived from a “molecular switch” within a selective mGlu7 NAM chemotype. VU6027459 displayed CNS penetration in both mice (Kp = 2.74) and rats (Kp= 4.78), it was orally bioavailable in rats (%F = 69.5), a...

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Veröffentlicht in:ACS medicinal chemistry letters 2020-09, Vol.11 (9), p.1773-1779
Hauptverfasser: Reed, Carson W, Kalbfleisch, Jacob J, Wong, Madison J, Washecheck, Jordan P, Hunter, Ashton, Rodriguez, Alice L, 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 discovery of the first selective and CNS penetrant mGlu7 PAM (VU6027459) derived from a “molecular switch” within a selective mGlu7 NAM chemotype. VU6027459 displayed CNS penetration in both mice (Kp = 2.74) and rats (Kp= 4.78), it was orally bioavailable in rats (%F = 69.5), and undesired activity at DAT was ablated.
ISSN:1948-5875
1948-5875
DOI:10.1021/acsmedchemlett.0c00432