Discovery of PIPE-359, a Brain-Penetrant, Selective M
| العنوان: | Discovery of PIPE-359, a Brain-Penetrant, Selective M |
|---|---|
| المؤلفون: | Thomas O, Schrader, Yifeng, Xiong, Ariana O, Lorenzana, Alexander, Broadhead, Karin J, Stebbins, Michael M, Poon, Christopher, Baccei, Daniel S, Lorrain |
| المصدر: | ACS Med Chem Lett |
| سنة النشر: | 2020 |
| الوصف: | [Image: see text] The discovery of PIPE-359, a brain-penetrant and selective antagonist of the muscarinic acetylcholine receptor subtype 1 is described. Starting from a literature-reported M(1) antagonist, linker replacement and structure–activity relationship investigations of the eastern 1-(pyridinyl)piperazine led to the identification of a novel, potent, and selective antagonist with good MDCKII-MDR1 permeability. Continued semi-iterative positional scanning facilitated improvements in the metabolic and hERG profiles, which ultimately delivered PIPE-359. This advanced drug candidate exhibited robust efficacy in mouse myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalitis (EAE), a preclinical model for multiple sclerosis. |
| تدمد: | 1948-5875 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=pmid________::3fa8ec81843f4909dda2e384fce0b703 https://pubmed.ncbi.nlm.nih.gov/33488977 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.pmid..........3fa8ec81843f4909dda2e384fce0b703 |
| قاعدة البيانات: | OpenAIRE |
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