57184-25-5Relevant articles and documents
Discovery of Novel Apigenin-Piperazine Hybrids as Potent and Selective Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors for the Treatment of Cancer
Long, Huan,Hu, Xiaolong,Wang, Baolin,Wang, Quan,Wang, Rong,Liu, Shumeng,Xiong, Fei,Jiang, Zhenzhou,Zhang, Xiao-Qi,Ye, Wen-Cai,Wang, Hao
, p. 12089 - 12108 (2021/09/06)
Poly (ADP-ribose) polymerase-1 (PARP-1) is a potential target for the discovery of chemosensitizers and anticancer drugs. Amentoflavone (AMF) is reported to be a selective PARP-1 inhibitor. Here, structural modifications and trimming of AMF have led to a series of AMF derivatives (9a-h) and apigenin-piperazine/piperidine hybrids (14a-p, 15a-p, 17a-h, and 19a-f), respectively. Among these compounds, 15l exhibited a potent PARP-1 inhibitory effect (IC50 = 14.7 nM) and possessed high selectivity to PARP-1 over PARP-2 (61.2-fold). Molecular dynamics simulation and the cellular thermal shift assay revealed that 15l directly bound to the PARP-1 structure. In in vitro and in vivo studies, 15l showed a potent chemotherapy sensitizing effect against A549 cells and a selective cytotoxic effect toward SK-OV-3 cells through PARP-1 inhibition. 15l·2HCl also displayed good ADME characteristics, pharmacokinetic parameters, and a desirable safety margin. These findings demonstrated that 15l·2HCl may serve as a lead compound for chemosensitizers and the (BRCA-1)-deficient cancer therapy.
Preparation method of Volasertib intermediate 1-cyclopropyl methyl piperazine
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Paragraph 0030; 0035, (2018/09/08)
The invention provides a preparation method of a Volasertib intermediate 1-cyclopropyl methyl piperazine. The preparation method comprises the following steps: S1, adding N-Boc-piperazine into an inert solvent and triethylamine or pyridine, dropwise adding cyclopropanecarbonyl chloride, adding water for extraction after the reaction ends, obtaining an organic phase, and concentrating the organic phase to remove an organic solvent to obtain a solid; S2, adding the solid obtained in S1 into an ether solvent, then adding sodium borohydride, dropwise adding boron trifluoride-diethyl ether for reaction, quenching the mixture, then extracting the mixture, and concentrating the mixture to remove an organic solvent to obtain a solid; S3, adding the solid obtained in S2 into an alcohol solvent, dropwise adding concentrated hydrochloric acid for reaction, alkalizing the mixture with sodium hydroxide or potassium hydroxide aqueous solution, and performing extraction and concentration in sequenceto obtain the compound 1-cyclopropyl methyl piperazine. The raw materials used in the preparation method are readily available, and the preparation method is low in cost, easy to operate, high in safety, high in product quality and yield, and convenient for large-scale production.
DIHYDROPTERIDINONE DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF
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Page/Page column 68, (2012/08/08)
Dihydroperidinone derivatives, preparation process and pharmaceutical use thereof are disclosed. Specially, new dihydroperidinone derivatives represented by general formula (I), wherein each substituent of the general formula (I) is defined as in the description, their preparation process, pharmaceutical compositions comprising said derivatives and their use as therapeutical agents, especially as Plk kinase inhibitors are disclosed.
