AI Article Synopsis
- - This letter focuses on optimizing a series of compounds known as 5-amino-thieno[2,3-c]pyridazine, specifically the development of VU0476406, a positive allosteric modulator (PAM).
- - VU0476406 is a significant tool for studying pharmacodynamics, allowing researchers to translate findings from rodent models to non-human primates (NHP).
- - The document reveals new information about the optimization process, as well as the pharmacological and drug metabolism and pharmacokinetics (DMPK) properties of VU0476406, including its relevance in a Parkinson's disease model.
Article Abstract
This letter describes the further chemical optimization of the 5-amino-thieno[2,3-c]pyridazine series (VU0467154/VU0467485) of M positive allosteric modulators (PAMs), developed via iterative parallel synthesis, culminating in the discovery of the non-human primate (NHP) in vivo tool compound, VU0476406 (8p). VU0476406 is an important in vivo tool compound to enable translation of pharmacodynamics from rodent to NHP, and while data related to a Parkinson's disease model has been reported with 8p, this is the first disclosure of the optimization and discovery of VU0476406, as well as detailed pharmacology and DMPK properties.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508548 | PMC |
| http://dx.doi.org/10.1016/j.bmcl.2017.04.043 | DOI Listing |
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