Discovery of a novel 2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide M positive allosteric modulator (PAM) chemotype
Authors
Temple
KJ
Kayla J
,
Engers
JL
Julie L
,
Long
MF
Madeline F
,
Watson
KJ
Katherine J
,
Chang
S
Sichen
,
Luscombe
VB
Vincent B
,
Jenkins
MT
Matthew T
,
Rodriguez
AL
Alice L
,
Niswender
CM
Colleen M
,
Bridges
TM
Thomas M
,
Conn
PJ
P Jeffrey
,
Engers
DW
Darren W
,
Lindsley
CW
Craig W
.
Bioorganic & medicinal chemistry letters. 2019 11 13; 30(3).
126812
Bioorganic & medicinal chemistry letters. 2019 11 13; 30(3).
126812
Abstract
This Letter details our efforts to discover structurally unique M PAMs containing 5,6-heteroaryl ring systems. In an attempt to improve the DMPK profiles of the 2,3-dimethyl-2H-indazole-5-carboxamide and 1-methyl-1H-benzo[d][1,2,3]triazole-6-carboxamide cores, we investigated a plethora of core replacements. This exercise identified a novel 2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide core that provided improved M PAM activity and CNS penetration.
Tags: 2019