67443-38-3Relevant articles and documents
Alkylsulfonamide-containing quinazoline derivatives as potent and orally bioavailable PI3Ks inhibitors
Hei, Yuan-Yuan,Zhang, San-Qi,Feng, Yifan,Wang, Jin,Duan, Weiming,Zhang, Hao,Mao, Shuai,Sun, Haopeng,Xin, Minhang
, (2019/06/08)
Phosphoinositide 3-kinases (PI3Ks) are regarded as promising targets for treatment of various cancers due to their roles in regulating cell proliferation, differentiation, migration, and survival. Here we report our efforts to develop potent and orally bioavailable PI3K inhibitors for the treatment of cancers. The alkylsulfonamide-containing quinazoline derivatives A1–A18 significantly inhibited PI3Kα, and cell proliferation among HCT-116, MCF-7 and SU-DHL-6 cell lines. The optimal compound A1 displayed potent inhibitory activity against PI3Kα (IC50 = 4.5 nM), PI3Kβ (IC50 = 4.5 nM), PI3Kγ (IC50 = 4.5 nM), PI3Kδ (IC50 = 4.5 nM) and significantly inhibited the growth of HCT-116, MCF-7 and SU-DHL-6 cell lines with IC50 values of 0.82 μM, 0.99 μM and 0.19 μM, respectively. Western blot analysis demonstrated A1 significantly suppressed the phosphorylation of AKTS473 in a dose-dependent manner. Furthermore, A1 could markedly inhibit cancer growth at the dose of 25 mg/kg in nude mouse HCT-116 xenograft model in vivo without causing significant weight loss or toxicity.
Large-scale solvent-free chlorination of hydroxy-pyrimidines,-pyridines,- pyrazines and-amides using equimolar POCl3
Wang, Han,Wen, Kun,Wang, Le,Xiang, Ye,Xu, Xiaocheng,Shen, Yongjia,Sun, Zhihua
experimental part, p. 4533 - 4544 (2012/06/30)
Chlorination with equimolar POCl3 can be efficiently achieved not only for hydroxypyrimidines, but also for many other substrates such as 2-hydroxy-pyridines,-quinoxalines, or even-amides. The procedure is solvent-free and involves heating in a sealed reactor at high temperatures using one equivalent of pyridine as base. It is suitable for large scale (multigram) batch preparations.
NOVEL PYRIDOPYRIMIDINE DERIVATIVES AND USE THEREOF
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Page/Page column 17, (2012/09/25)
The invention provides novel substituted pyridopyrimidines represented by Formula I or a pharmaceutically acceptable salt, solvate, polymorph, ester, tautomer or prodrug thereof, and a composition comprising these compounds. The compounds provided can be used as inhibitors of the phosphoinositide 3′ OH kinase family (PI3K) for the treatment of inflammatory diseases, cancer, cardiovascular diseases, allergy, asthma and autoimmune disorders.
