Challenges in the development of an M(4) PAM in vivo tool compound: The discovery of VU0467154 and unexpected DMPK profiles of close analogs

This letter describes the chemical optimization of a novel series of M(4) positive allosteric modulators (PAMs) based on a 5-amino-thieno[2,3-c]pyridazine core, developed via iterative parallel synthesis, and culminating in the highly utilized rodent in vivo tool compound, VU0467154 (5). This is the...

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Published in:Bioorg Med Chem Lett
Main Authors: Wood, Michael R., Noetzel, Meredith J., Poslusney, Michael S., Melancon, Bruce J., Tarr, James C., Lamsal, Atin, Chang, Sichen, Luscombe, Vincent B., Weiner, Rebecca L., Cho, Hyekyung P., Bubser, Michael, Jones, Carrie K., Niswender, Colleen M., Wood, Michael W., Engers, Darren W., Brandon, Nicholas J., Duggan, Mark E., Conn, P. Jeffrey, Bridges, Thomas M., Lindsley, Craig W.
Format: Artigo
Language:Inglês
Published: 2016
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Online Access:https://ncbi.nlm.nih.gov/pmc/articles/PMC5340297/
https://ncbi.nlm.nih.gov/pubmed/27939174
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1016/j.bmcl.2016.11.086
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