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Discovery of a novel 2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide M4 positive allosteric modulator (PAM) chemotype.

Abstract：

:This Letter details our efforts to discover structurally unique M4 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 M4 PAM activity and CNS penetration.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Temple KJ,Engers JL,Long MF,Watson KJ,Chang S,Luscombe VB,Jenkins MT,Rodriguez AL,Niswender CM,Bridges TM,Conn PJ,Engers DW,Lindsley CW

doi

10.1016/j.bmcl.2019.126812

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

126812

issue

3

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(19)30781-4

journal_volume

30

pub_type

杂志文章

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