Brawn, Ryan A.; Cook, Andrew; Omoto, Kiyoyuki; Ke, Jiyuan; Karr, Craig; Colombo, Federico; Virrankoski, Milena; Prajapati, Sudeep; Reynolds, Dominic; Bolduc, David M.; Nguyen, Tuong-Vi; Gee, Patricia; Borrelli, Deanna; Caleb, Benjamin; Yao, Shihua; Irwin, Sean; Larsen, Nicholas A.; Selvaraj, Anand; Zhao, Xuesong; Ioannidis, Stephanos published their research in ACS Medicinal Chemistry Letters in 2021. The article was titled 《Discovery of Aminopyrazole Derivatives as Potent Inhibitors of Wild-Type and Gatekeeper Mutant FGFR2 and 3》.Product Details of 3764-01-0 The article contains the following contents:
Fibroblast growth factor receptors (FGFR) 2 and 3 have been established as drivers of numerous types of cancer with multiple drugs approved or entering late stage clin. trials. A limitation of current inhibitors is vulnerability to gatekeeper resistance mutations. Using a combination of targeted high-throughput screening and structure-based drug design, we have developed a series of aminopyrazole based FGFR inhibitors that covalently target a cysteine residue on the P-loop of the kinase. The inhibitors show excellent activity against the wild-type and gatekeeper mutant versions of the enzymes. Further optimization using SAR anal. and structure-based drug design led to analogs with improved potency and drug metabolism and pharmacokinetics properties. The results came from multiple reactions, including the reaction of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Product Details of 3764-01-0)
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.Product Details of 3764-01-0
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia