Discovery of VU6027459: A First-in-Class Selective and CNS Penetrant mGlu Positive Allosteric Modulator Tool Compound
Authors
Reed
CW
Carson W
,
Kalbfleisch
JJ
Jacob J
,
Wong
MJ
Madison J
,
Washecheck
JP
Jordan P
,
Hunter
A
Ashton
,
Rodriguez
AL
Alice L
,
Blobaum
AL
Anna L
,
Conn
PJ
P Jeffrey
,
Niswender
CM
Colleen M
,
Lindsley
CW
Craig W
.
ACS medicinal chemistry letters. 2020 8 20; 11(9).
1773-1779
ACS medicinal chemistry letters. 2020 8 20; 11(9).
1773-1779
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