23967-57-9Relevant articles and documents
Design, synthesis, and biological evaluation of benzo[b]thiophene 1,1-dioxide derivatives as potent STAT3 inhibitors
Li, Wen-Zhen,Xi, Hui-Zhi,Wang, Yi-Jie,Ma, Hong-Bo,Cheng, Zhi-Qiang,Yang, Yu,Wu, Meng-Ling,Liu, Ting-Mei,Yang, Wen,Wang, Qin,Liao, Meng-Ya,Xia, Yong,Zhang, Yi-Wen
, p. 835 - 849 (2021/09/02)
As a member of the signal transducer and activator of transcription (STAT) family, STAT3 plays a critical role in several biological pathways such as cell proliferation, migration, survival, and differentiation. Due to abnormal continuous activation in tumors, inhibition of STAT3 has emerged as an attractive approach for the treatment of various cancer cells. Herein, we report a series of novel STAT3 inhibitors based on benzo[b]thiophene 1,1-dioxide scaffold and evaluated their anticancer potency. Among them, compound 8b exhibited the best activity against cancer cells. Compound 8b induced apoptosis and blocked the cell cycle. Meanwhile, 8b reduced intracellular ROS content and caused the loss of mitochondrial membrane potential. Further research revealed that 8b significantly blocked STAT3 phosphorylation and STAT3-dependent dual-luciferase reporter gene experiments showed that compound 8b has a marked inhibition of STAT3-mediated Firefly luciferase activity. Molecular modeling studies revealed compound 8b occupied the pocket well with the SH2 domain in a favorable conformation.
Discovery of fluorescent coumarin-benzo[b]thiophene 1, 1-dioxide conjugates as mitochondria-targeting antitumor STAT3 inhibitors
Cai, Guiping,Yu, Wenying,Song, Dongmei,Zhang, Wenda,Guo, Jianpeng,Zhu, Jiawen,Ren, Yuhao,Kong, Lingyi
, p. 236 - 251 (2019/05/02)
STAT3 has been extensively studied as a potential antitumor target. Though studies on regulating STAT3 mainly focus on the inhibition of STAT3 phosphorylation at Tyr705 residue, the phosphorylation at Ser727 residue of STAT3 protein is also closely associated with the mitochondrial import of STAT3 protein. N, N-diethyl-7-aminocoumarin is a fluorescent mitochondria-targeting probe. In this study, a series of STAT3 inhibitors were developed by connecting N, N-diethyl-7-aminocoumarin fluorophore with benzo [b]thiophene 1, 1-dioxide moiety. All designed compounds displayed potent anti-proliferative activity against cancer cells. The representative compound 7a was mainly accumulated in mitochondria visualized by its fluorescence. STAT3 phosphorylation was inhibited by compound 7a at both Tyr705 and Ser727 residues. Compound 7a inhibited STAT3 phosphorylation whereas had no influence on the phosphorylation levels of STAT1, JAK2, Src and Erk1/2, indicating good selectivity of compound 7a. Moreover, compound 7a down-regulated the expression of STAT3 target genes Bcl-2 and Cyclin D1, increased ROS production and remarkably reduced the mitochondrial membrane potential to induce mitochondrial apoptotic pathway. Furthermore, compound 7a in vivo suppressed breast cancer 4T1 implanted tumor growth. Taken together, these results highlighted that compound 7a might be a promising mitochondria-targeting STAT3 inhibitor for cancer therapy.
Preparation method of 4-chloro-1-benzothiophene-2-carboxylic acid
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Paragraph 0020-0025, (2017/08/27)
The invention relates to the technical field of medical intermediates and particularly relates to a preparation method of 4-chloro-1-benzothiophene-2-carboxylic acid. The preparation method comprises the steps of adding water and potassium hydroxide into a reaction flask, stirring to dissolve so as to obtain a potassium hydroxide solution, dropwise adding mercaptoacetic acid at room temperature, sequentially adding 2,6-dichlorobenzaldehyde, xylene and TBAB, intensely stirring, heating to generate reflux, maintaining the reaction for 3 hours, cooling to 85 DEG C, adding water to dissolve solids, pouring the solution into a separating funnel, standing to layer, transferring a water layer into the reaction flask, dropwise adding hydrochloric acid while hot until the pH is less than 2, stirring for half an hour, filtering, rinsing filter cake with hot water, draining, transferring the filter cake into a drying oven, blowing, and drying so as to obtain 4-chloro-1-benzothiophene-2-carboxylic acid. Pressure-resistant equipment is not used, and the operation is simple and convenient, so that the preparation method is applicable to industrial production; and by taking xylene as a solvent, impurities generated in the reaction process are dissolved into xylene, are eliminated after the reaction and do not need to be removed by virtue of flammable and combustible ethyl ether, so that the potential safety hazard during the production is eliminated.
