149777-86-6Relevant articles and documents
Discovery of Aminopyrazole Derivatives as Potent Inhibitors of Wild-Type and Gatekeeper Mutant FGFR2 and 3
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
supporting information, p. 93 - 98 (2020/12/21)
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 clinical 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 analysis and structure-based drug design led to analogues with improved potency and drug metabolism and pharmacokinetics properties.
Direct Synthesis of Alkenylboronates from Alkenes and Pinacol Diboron via Copper Catalysis
Lu, Wenkui,Shen, Zengming
supporting information, p. 142 - 146 (2019/01/11)
We report an efficient approach for the direct synthesis of alkenylboronates using copper catalysis. The Cu/TEMPO catalyst system (where TEMPO = (2,2,6,6-tetramethylpiperidin-1-yl)oxyl) exhibits both excellent reactivity and selectivity for the synthesis of alkenylboronates, starting from inexpensive and abundant alkenes and pinacol diboron. This approach allows for the direct functionalization of both aromatic and aliphatic terminal alkenes. Mechanistic experiments suggest that the alkenylboronates arise from oxyboration intermediates.
PYRIMIDINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF CANCER
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Page/Page column 38-39, (2008/06/13)
This invention relates to novel compounds (I) and processes for their preparation, methods of treating diseases, particularly cancer, comprising administering said compounds, and methods of making pharmaceutical compositions for the treatment or prevention of disorders, particularly cancer.