503-69-5Relevant articles and documents
Continuous synthesis method of hydroxypyrimidine compound
-
Paragraph 0012; 0030; 0034, (2020/07/28)
The invention discloses a continuous synthesis method of a hydroxypyrimidine compound. The method comprises the steps: carrying out continuous reaction on organic amine and a 50% cyanamide aqueous solution in a micro-reactor, introducing the reaction solution into a liquid separator for continuous phase splitting, carrying out continuous ring closing on a guanidine solution and alpha-alkyl acetoacetate in a second micro-reactor, washing the reaction solution with water, and desolventizing to obtain a target product. The method is based on the concept of green chemistry, the comprehensive costof raw materials is far lower than that of traditional methods, no salt-containing wastewater is generated, and treatment is easy; traditional solid-liquid separation is avoided, automatic productionis facilitated, and the safety and environmental protection level of the device is improved; continuous synthesis is adopted, decomposition of an intermediate is avoided, the total yield is larger than 82%, and the product content reaches 98%.
Discovery of 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine inhibitors of Erk2
Blake, James F.,Gaudino, John J.,De Meese, Jason,Mohr, Peter,Chicarelli, Mark,Tian, Hongqi,Garrey, Rustam,Thomas, Allen,Siedem, Christopher S.,Welch, Michael B.,Kolakowski, Gabrielle,Kaus, Robert,Burkard, Michael,Martinson, Matthew,Chen, Huifen,Dean, Brian,Dudley, Danette A.,Gould, Stephen E.,Pacheco, Patricia,Shahidi-Latham, Sheerin,Wang, Weiru,West, Kristina,Yin, Jianping,Moffat, John,Schwarz, Jacob B.
, p. 2635 - 2639 (2014/06/09)
The discovery and optimization of a series of tetrahydropyridopyrimidine based extracellular signal-regulated kinase (Erks) inhibitors discovered via HTS and structure based drug design is reported. The compounds demonstrate potent and selective inhibition of Erk2 and knockdown of phospho-RSK levels in HepG2 cells and tumor xenografts.
Synthesis of novel strobilurin-pyrimidine derivatives and their antiproliferative activity against human cancer cell lines
Chai, Baoshan,Wang, Shuyang,Yu, Wenquan,Li, Huichao,Song, Chuanjun,Xu, Ying,Liu, Changling,Chang, Junbiao
, p. 3505 - 3510 (2013/07/28)
A series of new strobilurin-pyrimidine analogs were designed and synthesized based on the structures of our previously discovered antiproliferative compounds I and II. Biological evaluation with two human cancer cell lines (A549 and HL60) showed that most of these compounds possessed moderate to potent antiproliferative activity. Two potent candidates (8f, IC50 = 2.2 nM and 11d, IC50 = 3.4 nM) were identified with nanomolar activity against leukemia cancer cell line HL60 for further development. This activity represents a 1000- to 2500-fold improvement compared to the parent compounds I and II and is 20- to 30-fold better than the chemotherapy drug, doxorubicin. The present work provides strong incentive for further development of these strobilurin-pyrimidine analogs as potential antitumor agents for the treatment of leukemia.
