Discovery of VU6027459: A First-in-Class Selective and CNS Penetrant mGlu Positive Allosteric Modulator Tool Compound
AUTHORS
Reed
CWCarson W ,
Kalbfleisch
JJJacob J ,
Wong
MJMadison J ,
Washecheck
JPJordan P ,
Hunter
AAshton ,
Rodriguez
ALAlice L ,
Blobaum
ALAnna L ,
Conn
PJP Jeffrey ,
Niswender
CMColleen M ,
Lindsley
CWCraig W .
ACS medicinal chemistry letters. 2020 8 20; 11(9).
1773-1779
- PMID: 32944146[PubMed].
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.
Tags: 2020