7682-18-0Relevant articles and documents
Design, synthesis and biological evaluation of novel pteridinone derivatives possessing a sulfonyl moiety as potent dual inhibitors of PLK1 and BRD4
Chen, Fei,Cui, Xinhua,Gao, Zhanfeng,Gong, Ping,Hou, Yunlei,Li, Zhiwei,Liu, Jiuyu,Liu, Yajing,Qin, Mingze,Wang, Shihui,Wang, Yu,Wang, Yuehan,Zhao, Yanfang
, p. 1246 - 1259 (2022/02/07)
The simultaneous inhibition of PLK1 and BRD4 by a single molecule could lead to the development of an effective therapeutic strategy for a variety of diseases in which PLK1 and BRD4 are implicated. Herein, two series of novel pteridinone derivatives possessing a sulfonyl moiety were designed, synthesized and evaluated for their biological activity. Most compounds exhibited moderate to excellent cytotoxic activity against HCT116, PC3 and BT474 cell lines. Among them, the most promising compound B2 showed high antiproliferative effects on the three cell lines with IC50 values of 0.30 μM, 1.82 μM and 1.69 μM, respectively. In the enzymatic assay, B2 was identified as a potent PLK1 and BRD4 dual inhibitor (PLK1 IC50 = 6.3 nM, BRD4 IC50 = 179 nM). Further explorations in bioactivity were conducted to clarify the anticancer mechanism of compound B2. The results showed that compound B2 obviously inhibited the proliferation of HCT116 cell lines, induced a great decrease in the mitochondrial membrane potential leading to apoptosis of HCT116 cells and arrested the G2 phase of HCT116 cells.
Preparation method of (S)-(+)-2-aminobutanamide hydrochloride
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Paragraph 0043-0048; 0054-0059; 0065-0070; 0076-0081, (2020/08/02)
The invention discloses a preparation method of (S)-(+)-2-aminobutanamide hydrochloride, and relates to a preparation method of a levetiracetam key intermediate, and the method comprises the followingspecific steps: carrying out esterification reaction on L-2-aminobutyric acid serving as a starting material and thionyl chloride, and concentrating part of solvent after the reaction is finished; introducing ammonia gas to neutralize generated hydrogen chloride and residual thionyl chloride; and filtering, introducing ammonia gas, and carrying out an ammonolysis reaction to obtain the (S)-2-aminobutanamide hydrochloride after the treating is finished. According to the preparation method, the starting material is simple and easy to obtain, the one-pot method is adopted, the atom utilization rate is high, operation is easy and convenient, and the obtained product quality is high.
Method for preparing levetiracetam
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Paragraph 0112-0116; 0129-0132, (2019/01/23)
The invention relates to the technical field of drug synthesis, and provides a method for preparing levetiracetam. The method includes the following steps: taking L-2-aminobutyric acid as a starting material, and preforming esterification with thionyl chloride to obtain (S)-2-methyl aminobutyrate hydrochloride; performing aminolysis reaction between the (S)-2-methyl aminobutyrate hydrochloride andammonia water to generate (S)-2-aminobutylamine hydrochloride; preforming acylation reaction between the(S)-2-aminobutylamine hydrochloride and the mixed solution of 4-chlorobutyryl chloride and dichloromethane; directly performing cyclization reaction between the intermediate product with the dichloromethane and tetrabutyl ammonium bromide to obtain a crude product of levetiracetam; and recrystallizing the crude product to generate the levetiracetam. The preparation method uses the easily-obtained starting material to ensure good reproducibility of the synthesis route, simple unit operationand economic accounting. The reaction in each step is easy to purify, the quality is controllable, and the reaction yield is greatly improved.
