938182-43-5Relevant articles and documents
Design, synthesis, and biological evaluation of novel thiazolyl substituted bis-pyrazole oxime derivatives with potent antitumor activities by selectively inducing apoptosis and ros in cancer cells
Xiong, Biao,Chen, Shi,Zhu, Peng,Huang, Meiling,Gao, Weijie,Zhu, Rui,Qian, Jianqiang,Peng, Yanfu,Zhang, Yanan,Dai, Hong,Ling, Yong
, p. 743 - 754 (2019/11/02)
Background: A large number of pyrazole derivatives have different biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic and antiepileptic activity. Among them, pyrazole oximes have attracted much attention due to their potential pharmacological activities, particularly anticancer activities. Objective: Our goal is to synthesize novel thiazolyl substituted bis-pyrazole oxime derivatives with potent antitumor activities by selectively inducing apoptosis and Reactive Oxygen Species (ROS) accumulation in cancer cells. Methods: Eighteen bis-pyrazole oximes were synthesized by conjugating thiazolyl substituted pyrazoles with pyrazoxime. The target compounds were characterized by1HNMR,13C NMR, and HRMS, and screened for their antiproliferative activity against four cancer cells in MTT assay. The most potent compound was examined for its inhibitory effect and ROS accumulation in both cancer cells HCT116 and normal intestinal epithelial cells CCD841. Finally, the most potent compound was further evaluated for its apoptotic induction by flow cytometry analysis and immunoblot analysis of apoptosis-related proteins and DNA damage proteins. Results: Most compounds displayed potent antiproliferative activity against four cancer cell lines in vitro, displaying potencies superior to 5-FU. In particular, the most potent compound 13l selectively inhibited proliferation of colorectal cancer HCT116 cells but not normal colon CCD841 cells. Furthermore, compound 13l also selectively promoted intracellular ROS accumulation in HCT116 which was involved in 13l inhibition of cancer cell proliferation and induction of cell apoptosis. Finally, compound 13l also dose-dependently induced cancer cell apoptosis by regulating apoptotic and DNA damage related proteins expressions. Conclusion: Our synthetic bis-pyrazole oxime derivatives possess potent antitumor activities by selectively inducing apoptosis and ROS accumulation in cancer cells, which may hold great promise as therapeutic agents for the treatment of human cancers.
Fragment-based lead generation of 5-phenyl-1H-pyrazole-3-carboxamide derivatives as leads for potent factor xia inhibitors
Wei, Qunchao,Zheng, Zhichao,Zhang, Shijun,Zheng, Xuemin,Meng, Fancui,Yuan, Jing,Xu, Yongnan,Huang, Changjiang
, (2018/09/26)
FXIa is suggested as a major target for anticoagulant drug discovery because of reduced risk of bleeding. In this paper, we defined 5-phenyl-1H-pyrazole-3-carboxylic acid derivatives as privileged fragments for FXIa inhibitors' lead discovery. After repla
1. 3, 5 - tri-substituted pyrazole compound and its preparation method and application
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Paragraph 0114; 0115; 0116; 0118, (2017/04/18)
The invention discloses 1,3,5-trisubstituted pyrazole compounds, and a preparation method and application thereof. The structure of the compounds is shown as a general formula (I), and in the general formula (I), R1 is hydrogen, halogens, methyl or triflu
Base mediated 1,3-dipolar cycloaddition of α-substituted vinyl phosphonates with diazo compounds for synthesis of 3-pyrazolylphosphonates and 5-pyrazolcarboxylates
Goulioukina, Nataliya S.,Makukhin, Nikolay N.,Shinkarev, Egor D.,Grishin, Yuri K.,Roznyatovsky, Vitaly A.,Beletskaya, Irina P.
, p. 10000 - 10010 (2016/11/06)
5-Aryl-substituted pyrazol-3-ylphosphonates have been conveniently synthesized by 1,3-dipolar cycloaddition of 1-formamidovinylphosphonates and aryldiazomethanes under K2CO3/MeOH conditions at room temperature. These pyrazoles are formed in one pot via spontaneous elimination of formamide. Basic conditions prevent competitive formation of cyclopropylphosphonates. 3-Aryl substituted pyrazol-5-carboxylates can be synthesized by the same methodology from 1-arylvinylphosphonates and ethyl diazoacetate, although a stronger base NaH is necessary to ensure the success of the aromatization stage with the elimination of the diethoxylphosphoryl moiety.
Cascade regioselective synthesis of pyrazoles from nitroallylic acetates and N-tosyl hydrazine
Shao, Nana,Chen, Tong,Zhang, Taotao,Zhu, Huajian,Zheng, Qunxiong,Zou, Hongbin
, p. 795 - 799 (2014/01/23)
A simple, practical, and regioselective synthetic protocol for the formation of pyrazoles was developed. Unlike all other previously reported reactions of nitroallylic acetates, this process was initiated by a S N2 reaction at the electrophilic γ site. A plausible mechanism for the cascade SN2-Michael synthesis is proposed.
Pyrazole-oxadiazole conjugates: Synthesis, antiproliferative activity and inhibition of tubulin polymerization
Kamal, Ahmed,Shaik, Anver Basha,Polepalli, Sowjanya,Santosh Reddy, Vangala,Bharath Kumar,Gupta, Soma,Rama Krishna,Nagabhushana, Ananthamurthy,Mishra, Rakesh K.,Jain, Nishant
, p. 7993 - 8007 (2015/02/18)
A number of pyrazole-oxadiazole conjugates were synthesized and evaluated for their ability to function as antiproliferative agents on various human cancer cell lines. These conjugates are comprised of pyrazole and oxadiazole scaffolds closely attached to each other without any spacer as two structural classes. The Type I class has a trimethoxy substituent and the type II class has a 3,4-(methylenedioxy) substituent on their A rings. Among these conjugates, 11a, 11d and 11f manifest potent cytotoxicity with IC50values ranging from 1.5 μM to 11.2 μM and inhibit tubulin polymerization with IC50values of 1.3 μM, 3.9 μM and 2.4 μM respectively. The cell cycle assay showed that treatment with these conjugates results in accumulation of cells in the G2/M phase and disrupts the microtubule network. Elucidation of zebrafish embryos revealed that the conjugates cause developmental defects. Molecular docking simulations determined the binding modes of these potent conjugates at the colchicine site of tubulin.
Synthesis, Structure-Activity Relationship, and Pharmacophore Modeling Studies of Pyrazole-3-Carbohydrazone Derivatives as Dipeptidyl Peptidase IV Inhibitors
Wu, Deyan,Jin, Fangfang,Lu, Weiqiang,Zhu, Jin,Li, Cui,Wang, Wei,Tang, Yun,Jiang, Hualiang,Huang, Jin,Liu, Guixia,Li, Jian
experimental part, p. 897 - 906 (2012/07/27)
Type 2 diabetes mellitus (T2DM) is a metabolic disease and a major challenge to healthcare systems around the world. Dipeptidyl peptidase IV (DPP-4), a serine protease, has been rapidly emerging as an effective therapeutic target for the treatment for T2DM. In this study, a series of novel DPP-4 inhibitors, featuring the pyrazole-3-carbohydrazone scaffold, have been discovered using an integrated approach of structure-based virtual screening, chemical synthesis, and bioassay. Virtual screening of SPECS Database, followed by enzymatic activity assay, resulted in five micromolar or low-to-mid-micromolar inhibitory level compounds (1-5) with different scaffold. Compound 1 was selected for the further structure modifications in considering inhibitory activity, structural variability, and synthetic accessibility. Seventeen new compounds were synthesized and tested with biological assays. Nine compounds (6e, 6g, 6k-l, and 7a-e) were found to show inhibitory effects against DPP-4. Molecular docking models give rational explanation about structure-activity relationships. Based on eight DPP-4 inhibitors (1-5, 6e, 6k, and 7d), the best pharmacophore model hypo1 was obtained, consisting of one hydrogen bond donor (HBD), one hydrogen bond acceptor (HBA), and two hydrophobic (HY) features. Both docking models and pharmacophore mapping results are in agreement with pharmacological results. The present studies give some guiding information for further structural optimization and are helpful for future DPP-4 inhibitors design.
Design and synthesis of novel pyrazole-based Lp-PLA2 inhibitors
Wang, Yi,Xu, Weiren,Shao, Hua,Xie, Yafei,Wang, Jianwu
experimental part, p. 2039 - 2048 (2012/03/26)
A series of novel pyrazole-based lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitors have been designed and synthetized by a variety of acetophenones via a 10-step convergent approach. The synthetic approach is carefully opt
Synthesis of pyrazole-3-carboxylates and pyrazole-1,5-dicarboxylates by one-pot cyclization of hydrazone dianions with diethyl oxalate
Dang, Tung T.,Dang, Tuan T.,Fischer, Christine,G?rls, Helmar,Langer, Peter
, p. 2207 - 2215 (2008/09/18)
The one-pot cyclization of hydrazone dianions with diethyl oxalate allows a convenient synthesis of pyrazole-3-carboxylates and pyrazole-1,5-dicarboxylates.
