Discovery and SAR of a novel series of potent, CNS penetrant M(4) PAMs based on a non-enolizable ketone core: Challenges in disposition

This letter describes the chemical optimization of a novel series of M(4) PAMs based on a non-enolizable ketone core, identified from an MLPCN functional high-throughput screen. The HTS hit was potent, selective and CNS penetrant; however, the compound was highly cleared in vitro and in vivo. SAR pr...

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Wedi'i Gadw mewn:
Manylion Llyfryddiaeth
Cyhoeddwyd yn:Bioorg Med Chem Lett
Prif Awduron: Wood, Michael R., Noetzel, Meredith J., Tarr, James C., Rodriguez, Alice L., Lamsal, Atin, Chang, Sichen, Foster, Jarrett J., Smith, Emery, Chase, Peter, Hodder, Peter S., Engers, Darren W., Niswender, Colleen M., Brandon, Nicholas J., Wood, Michael W., Duggan, Mark E., Conn, P. Jeffrey, Bridges, Thomas M., Lindsley, Craig W.
Fformat: Artigo
Iaith:Inglês
Cyhoeddwyd: 2016
Pynciau:
Article
Mynediad Ar-lein:https://ncbi.nlm.nih.gov/pmc/articles/PMC4987221/
https://ncbi.nlm.nih.gov/pubmed/27476142
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1016/j.bmcl.2016.07.042
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