In 2017,Stepan, Antonia F.; Claffey, Michelle M.; Reese, Matthew R.; Balan, Gayatri; Barreiro, Gabriela; Barricklow, Jason; Bohanon, Michael J.; Boscoe, Brian P.; Cappon, Gregg D.; Chenard, Lois K.; Cianfrogna, Julie; Chen, Laigao; Coffman, Karen J.; Drozda, Susan E.; Dunetz, Joshua R.; Ghosh, Somraj; Hou, Xinjun; Houle, Christopher; Karki, Kapil; Lazzaro, John T.; Mancuso, Jessica Y.; Marcek, John M.; Miller, Emily L.; Moen, Mark A.; O’Neil, Steven; Sakurada, Isao; Skaddan, Marc; Parikh, Vinod; Smith, Deborah L.; Trapa, Patrick; Tuttle, Jamison B.; Verhoest, Patrick R.; Walker, Daniel P.; Won, Annie; Wright, Ann S.; Whritenour, Jessica; Zasadny, Kenneth; Zaleska, Margaret M.; Zhang, Lei; Shaffer, Christopher L. published 《Discovery and Characterization of (R)-6-Neopentyl-2-(pyridin-2-ylmethoxy)-6,7-dihydropyrimido[2,1-c][1,4]oxazin-4(9H)-one (PF-06462894), an Alkyne-Lacking Metabotropic Glutamate Receptor 5 Negative Allosteric Modulator Profiled in both Rat and Nonhuman Primates》.Journal of Medicinal Chemistry published the findings.Related Products of 31106-82-8 The information in the text is summarized as follows:
We previously observed a cutaneous type IV immune response in nonhuman primates (NHP) with the mGlu5 neg. allosteric modulator (NAM) 7. To determine if this adverse event was chemotype- or mechanism-based, we evaluated a distinct series of mGlu5 NAMs. Increasing the sp3 character of high-throughput screening hit 40 afforded a novel morpholinopyrimidone mGlu5 NAM series. Its prototype, (R)-6-neopentyl-2-(pyridin-2-ylmethoxy)-6,7-dihydropyrimido[2,1-c][1,4]oxazin-4(9H)-one (PF-06462894, 8), possessed favorable properties and a predicted low clin. dose (2 mg twice daily). Compound 8 did not show any evidence of immune activation in a mouse drug allergy model. Addnl., plasma samples from toxicol. studies confirmed that 8 did not form any reactive metabolites. However, 8 caused the identical microscopic skin lesions in NHPs found with 7, albeit with lower severity. Holistically, this work supports the hypothesis that this unique toxicity may be mechanism-based although addnl. work is required to confirm this and determine clin. relevance. After reading the article, we found that the author used 2-(Bromomethyl)pyridine hydrobromide(cas: 31106-82-8Related Products of 31106-82-8)
2-(Bromomethyl)pyridine hydrobromide(cas: 31106-82-8) belongs to pyridine. Pyridine is a relatively complex molecule and exhibits a number of different bands in IR spectra. Among others, the bands characterizing the ν8a and ν19b modes have been found to be sensitive to the coordination or protonation of the molecule. Note that the band that is diagnostic for the PyH+ ion at about 1545 cm− 1 (ν19b mode) does not overlap with any of the other bands.Related Products of 31106-82-8