Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu1
Authors
Manka
JT
Jason T
,
Rodriguez
AL
Alice L
,
Morrison
RD
Ryan D
,
Venable
DF
Daryl F
,
Cho
HP
Hyekyung P
,
Blobaum
AL
Anna L
,
Daniels
JS
J Scott
,
Niswender
CM
Colleen M
,
Conn
PJ
P Jeffrey
,
Lindsley
CW
Craig W
,
Emmitte
KA
Kyle A
.
Bioorganic & medicinal chemistry letters. 2013 7 23; 23(18).
5091-6
Bioorganic & medicinal chemistry letters. 2013 7 23; 23(18).
5091-6
Abstract
Development of SAR in an octahydropyrrolo[3,4-c]pyrrole series of negative allosteric modulators of mGlu1 using a functional cell-based assay is described in this Letter. The octahydropyrrolo[3,4-c]pyrrole scaffold was chosen as an isosteric replacement for the piperazine ring found in the initial hit compound. Characterization of selected compounds in protein binding assays was used to identify the most promising analogs, which were then profiled in P450 inhibition assays in order to further assess the potential for drug-likeness within this series of compounds.
Tags: 2013