84145-43-7Relevant articles and documents
Design, synthesis and anticancer activity of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-1,2,3-thiadiazoles as microtubule-destabilizing agents
Wang, Chao,Wang, Zeyu,Gao, Minghuan,Li, Yuelin,Zhang, Yujing,Bao, Kai,Wu, Yingliang,Guan, Qi,Zuo, Daiying,Zhang, Weige
, (2020/12/21)
Hereby, we report our efforts on discovery and optimization of a new series of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-1,2,3-thiadiazoles as new microtubule-destabilizing agents along our previous study. Guided by docking model analysis, we introduced the 1,2,3-thiadiazole moiety containing the hydrogen-bond acceptors as B-ring of XRP44X analogues. Extensive structure modifications were performed to investigate the detailed structure and activity relationships (SARs). Some compounds exhibited potent antiproliferative activities against three human cancer cell lines (SGC-7901, A549 and HeLa). The compound 5m exhibited the highest potency against the three cancer cell lines. The tubulin polymerization experiments indicated that compound 5m effectively inhibited the tubulin polymerization, and immunostaining assay revealed that it significantly disrupted microtubule dynamics. Moreover, cell cycle studies revealed that compound 5m dramatically arrested cell cycle progression at G2/M phase.
Design, synthesis and evaluation of antiproliferative and antitubulin activities of 5-methyl-4-aryl-3-(4-arylpiperazine-1-carbonyl)-4H-1,2,4-triazoles
Wang, Chao,Li, Yuelin,Liu, Tong,Wang, Zeyu,Zhang, Yujing,Bao, Kai,Wu, Yingliang,Guan, Qi,Zuo, Daiying,Zhang, Weige
, (2020/10/12)
A series of novel 5-methyl-4-aryl-3-(4-arylpiperazine-1-carbonyl)-4H-1,2,4-triazoles possessing 1,2,4-triazole as the hydrogen-bond acceptor were designed, synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. Some of them exhibited moderate activities in vitro against the three cancer cell lines including SGC-7901, A549 and HeLa. Compound 6e exhibited the highest potency against the three cancer cell lines. Moreover, the tubulin polymerization experiments indicated that compound 6e could inhibit the tubulin polymerization. Immunofluorescence study and cell cycle analysis clearly revealed compound 6e could disrupt intracellular microtubule organization, arrest cell cycle at the G2/M phase. In addition, molecular docking analysis demonstrated the interaction of compound 6e at the colchicine-binding site of tubulin. These preliminary results suggested that compound 6e is a new colchicine binding site inhibitor and worthy of further investigation.
Preparation process of posaconazole intermediate 1-(4-hydroxyphenyl)-4-(4-aminophenyl)piperazine
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Paragraph 0027, (2018/06/23)
The invention relates to the technical field of chemical medicine synthesis, in particular to a preparation process of posaconazole intermediate 1-(4-hydroxyphenyl)-4-(4-aminophenyl)piperazine. The preparation process provided by the invention comprises the following steps of a, preparing methoxyphenyl piperazine hydrochloride; b, preparing p-hydroxyphenyl piperazine hydrobromide; c, preparing 1-(4-hydroxyphenyl)-4-(4-nitrophenyl)piperazine; d, preparing a crude product of 1-(4-hydroxyphenyl)-4-(4-aminophenyl)piperazine; e, purifying a product. Cheap solvents and high-activity nickel catalystsare selected and used; low-pressure hydrogenation reaction is used; the raw material cost is greatly reduced; important links such as nickel ion removal and aluminum ion removal are used for post treatment; the product quality reaches the content of 99.2 percent; the single maximum noise peak value is less than 0.1 percent; the total noise peak value is less than 1.0 percent; the home and abroadmarket competitive power of the product is greatly enhanced.
