16013-85-7Relevant articles and documents
Optimization of 4,6-Disubstituted Pyrido[3,2-d]pyrimidines as Dual MNK/PIM Inhibitors to Inhibit Leukemia Cell Growth
Han, Yu,Zhang, Huimin,Wang, Shuxiang,Li, Bo,Xing, Kun,Shi, Yuntao,Cao, Hongxue,Zhang, Jian,Tong, Tong,Zang, Jie,Guan, Lihong,Gao, Xiaoxiao,Wang, Yuetong,Liu, Dan,Huang, Min,Jing, Yongkui,Zhao, Linxiang
, p. 13719 - 13735 (2021/10/01)
Mitogen-activated protein kinase-interacting kinases (MNKs) and provirus integration in maloney murine leukemia virus kinases (PIMs) are downstream enzymes of cell proliferation signaling pathways associated with the resistance of tyrosine kinase inhibitors. MNKs and PIMs have complementary effects to regulate cap-dependent translation of oncoproteins. Dual inhibitors of MNKs and PIMs have not been developed. We developed a novel 4,6-disubstituted pyrido[3,2-d]pyrimidine compound 21o with selective inhibition of MNKs and PIMs. The IC50’s of 21o to inhibit MNK1 and MNK2 are 1 and 7 nM and those to inhibit PIM1, PIM2, and PIM3 are 43, 232, and 774 nM, respectively. 21o inhibits the growth of myeloid leukemia K562 and MOLM-13 cells with GI50’s of 2.1 and 1.2 μM, respectively. 21o decreases the levels ofp-eIF4E andp-4EBP1, the downstream products of MNKs and PIMs, as well as cap-dependent proteins c-myc, cyclin D1, and Mcl-1. 21o inhibits the growth of MOLM-13 cell xenografts without causing evident toxicity. 21o represents an innovative dual MNK/PIM inhibitor with a good pharmacokinetic profile.
NITRATION
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Page/Page column 36; 37; 49; 39; 53, (2020/05/28)
The present invention relates to a process for preparing a nitrated compound, comprising the step of reacting a compound (A) comprising at least one substituted or unsubstituted aromatic or heteroaromatic ring, wherein said heteroaromatic ring comprises at least one heteroatom selected from the group consisting of oxygen, sulfur, phosphor, selenium and nitrogen, with a compound of formula (I) wherein Y is selected from the group consisting of hydrogen and nitro.
Preparation method of 2,6-dichloro-3-nitropyridine
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Paragraph 0040-0045, (2019/10/01)
The invention relates to a 2,6-Dichloro-3-Preparation method of nitropyridine. The method uses 2-Nitroacetate and 2-Halogenated acrylates are catalyzed by organic bases for 1,4-Addition reaction followed by cyclization reaction with ammonia to obtain 2,6-Dihydroxy-3-Nitropyridine is then reacted with a chlorinating reagent to produce 2,6-Dichloro-3-Nitropyridine. The invention does not use concentrated sulfuric acid and nitric acid, the used raw materials are cheap and easily available, the operation is simple and convenient, the conditions are mild, the amount of waste water is small, the invention is safe and environment-friendly and the cost is low.