Van de Poel, Amanda; Toledo-Sherman, Leticia; Breccia, Perla; Cachope, Roger; Bate, Jennifer R.; Angulo-Herrera, Ivan; Wishart, Grant; Matthews, Kim L.; Martin, Sarah L.; Peacock, Marcus; Barnard, Amy; Cox, Helen C.; Jones, Graham; McAllister, George; Vater, Huw; Esmieu, William; Clissold, Cole; Lamers, Marieke; Leonard, Philip; Jarvis, Rebecca E.; Blackaby, Wesley; Eznarriaga, Maria; Lazari, Ovadia; Yates, Dawn; Rose, Mark; Jang, Sung-Wook; Munoz-Sanjuan, Ignacio; Dominguez, Celia published their research in Journal of Medicinal Chemistry in 2021. The article was titled 《Structure-Based Exploration of Selectivity for ATM Inhibitors in Huntington’s Disease》.Safety of 2,4,6-Trichloropyrimidine The article contains the following contents:
Our group has recently shown that brain-penetrant ataxia telangiectasia-mutated (ATM) kinase inhibitors may have potential as novel therapeutics for the treatment of Huntington’s disease (HD). However, the previously described pyranone-thioxanthenes (e.g., 4) failed to afford selectivity over a vacuolar protein sorting 34 (Vps34) kinase, an important kinase involved with autophagy. Given that impaired autophagy has been proposed as a pathogenic mechanism of neurodegenerative diseases such as HD, achieving selectivity over Vps34 became an important objective for our program. Here, we report the successful selectivity optimization of ATM over Vps34 by using X-ray crystal structures of a Vps34-ATM protein chimera where the Vps34 ATP-binding site was mutated to approx. that of an ATM kinase. The morpholino-pyridone and morpholino-pyrimidinone series that resulted as a consequence of this selectivity optimization process have high ATM potency and good oral bioavailability and have lower mol. weight, reduced lipophilicity, higher aqueous solubility, and greater synthetic tractability compared to the pyranone-thioxanthenes. In addition to this study using 2,4,6-Trichloropyrimidine, there are many other studies that have used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Safety of 2,4,6-Trichloropyrimidine) was used in this study.
2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Safety of 2,4,6-Trichloropyrimidine
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia