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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Vydáno v:Bioorg Med Chem Lett
Hlavní autoři: 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.
Médium: Artigo
Jazyk:Inglês
Vydáno: 2016
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On-line přístup: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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