Discovery of a novel 2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide M positive allosteric modulator (PAM) chemotype
AUTHORS
Temple
KJKayla J ,
Engers
JLJulie L ,
Long
MFMadeline F ,
Watson
KJKatherine J ,
Chang
SSichen ,
Luscombe
VBVincent B ,
Jenkins
MTMatthew T ,
Rodriguez
ALAlice L ,
Niswender
CMColleen M ,
Bridges
TMThomas M ,
Conn
PJP Jeffrey ,
Engers
DWDarren W ,
Lindsley
CWCraig W .
Bioorganic & medicinal chemistry letters. 2019 11 13; 30(3).
126812
- PMID: 31784320[PubMed].
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