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

ABSTRACT: 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 (K_p = 2.74) and rats (K_p= 4.78), it was orally bioavailable in rats (%F = 69.5), and undesired activity at DAT was ablated.

SUBMITTER: Reed CW

PROVIDER: S-EPMC7488291 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Reed Carson W CW Kalbfleisch Jacob J JJ Wong Madison J MJ Washecheck Jordan P JP Hunter Ashton A Rodriguez Alice L AL Blobaum Anna L AL Conn P Jeffrey PJ Niswender Colleen M CM Lindsley Craig W CW

ACS medicinal chemistry letters 20200820 9

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. ...[more]

PMID: 32944146

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