Discovery of structurally distinct tricyclic M 4 positive allosteric modulator (PAM) chemotypes.

Kayla J Temple,Madeline F Long,Julie L Engers,Katherine J Watson,Sichen Chang,Vincent B Luscombe,Alice L Rodriguez,Colleen M Niswender,Thomas M Bridges,P Jeffrey Conn,Darren W Engers,Craig W Lindsley

Bioorganic & Medicinal Chemistry Letters（2020）

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摘要

•Discovery of novel 2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide-based M4 PAMs.•Broad survey of diverse heterocyclic cores.•Balanced human and rat M4 PAM potency with excellent CNS penetration.

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关键词

M4,Muscarinic acetylcholine receptor,Positive allosteric modulator (PAM),Structure activity relationship (SAR)

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