Discovery of PIPE-359, a Brain-Penetrant, Selective M1 Receptor Antagonist with Robust Efficacy in Murine MOG-EAE was written by Schrader, Thomas O.;Xiong, Yifeng;Lorenzana, Ariana O.;Broadhead, Alexander;Stebbins, Karin J.;Poon, Michael M.;Baccei, Christopher;Lorrain, Daniel S.. And the article was included in ACS Medicinal Chemistry Letters in 2021.Product Details of 38186-85-5 This article mentions the following:
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 M1 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 exptl. autoimmune encephalitis (EAE), a preclin. model for multiple sclerosis. In the experiment, the researchers used many compounds, for example, 2-Bromo-5-fluoro-3-methylpyridine (cas: 38186-85-5Product Details of 38186-85-5).
2-Bromo-5-fluoro-3-methylpyridine (cas: 38186-85-5) belongs to pyridine derivatives. Pyridine has a conjugated system of six π electrons that are delocalized over the ring. The molecule is planar and, thus, follows the Hückel criteria for aromatic systems. Many analogues of pyridine are known where N is replaced by other heteroatoms . Substitution of one C–H in pyridine with a second N gives rise to the diazine heterocycles (C4H4N2), with the names pyridazine, pyrimidine, and pyrazine.Product Details of 38186-85-5