58519-43-0Relevant academic research and scientific papers
Discovery and SAR study of piperidine-based derivatives as novel influenza virus inhibitors
Wang, Guoxin,Chen, Longjian,Xian, Tongmei,Liang, Yujie,Zhang, Xintao,Yang, Zhen,Luo, Ming
, p. 8048 - 8060 (2014)
A series of piperidine-based derivatives were identified as novel and potent inhibitors of the influenza virus through structural modification of a compound that was selected from a high-throughput screen. Various analogues were synthesized and confirmed as inhibitors. The structure-activity relationship (SAR) studies suggested that the ether linkage between the quinoline and piperidine is critical for the inhibitory activity. The optimized compound tert-butyl 4-(quinolin-4-yloxy)piperidine-1-carboxylate 11e had an excellent inhibitory activity against influenza virus infection from a variety of influenza virus strains, with EC50values as low as 0.05 μM. The selectivity index value (SI = MLD50/EC50) of 11e is over 160 000 based on cytotoxicity, measured by MTT assays of three cell lines. We carried out a time-of-addition experiment to delineate the mechanism of inhibition. The result indicates that 11e interferes with the early to middle stage of influenza virus replication.
Synthesis and biological evaluations of N′-substituted methylene-4-(quinoline-4-amino) benzoylhydrazides as potential anti-hepatoma agents
Fang, Meijuan,He, Fengming,Huang, Qingqing,Li, Baicun,Liu, Xiaoguang,Qiu, Yingkun,Wu, Tong,Wu, Zhen,Xue, Yuhua,Zhao, Taige,Zhu, Feifeng
, (2020)
In the effort to develop novel quinoline derivatives for the treatment of liver cancer, we synthesized a series of N′-Substituted methylene-4-(quinoline-4-amino) benzoylhydrazides and evaluated their biological activities as anticancer agents. Compounds 5
Discovery of a Nur77-mediated cytoplasmic vacuolation and paraptosis inducer (4-PQBH) for the treatment of hepatocellular carcinoma
Fang, Meijuan,He, Fengming,Huang, Jiangang,Li, Baicun,Liu, Jie,Liu, Shunzhi,Qiu, Yingkun,Wang, Wang,Wen, Fangfang,Wu, Tong,Wu, Zhen,Yang, Changming,Yao, Jie,Zeng, Jinzhang,Zhao, Taige
, (2022/02/19)
Nur77, an orphan nuclear receptor, has antitumor activity in hepatocellular carcinoma (HCC). However, its antitumor mechanisms of action in HCC are complicated and rarely reported. Our recent work demonstrated that certain quinoline-Schiff-base derivatives were good Nur77 mediators that exerted excellent anti-HCC activities in vitro and in vivo. Interestingly, these compounds shared similar chemical structures, but they displayed different Nur77-targeted anticancer mechanisms of action. As a continuous work, we synthesized a series of 4-(quinoline-4-amino) benzoylhydrazide derivatives and evaluated their anti-HCC activity and binding affinity to Nur77 in vitro. Compound 4-PQBH emerged as the best Nur77 binder (KD = 1.17 μM) and has potentially selective cytotoxicity to HCC cells. Mechanistically, 4-PQBH extensively induced caspase-independent cytoplasmic vacuolization and paraptosis through Nur77-mediated ER stress and autophagy. Moreover, 4-PQBH exhibited an effective xenograft tumor inhibition by modulating Nur77-dependent cytoplasmic vacuolation and paraptosis. This paper is the first to disclose that chemotherapeutic agents targeting Nur77-mediated cytoplasmic vacuolization and paraptosis may provide a promising strategy to combat HCC that frequently evade the apoptosis program.
Sustainable ppm level palladium-catalyzed aminations in nanoreactors under mild, aqueous conditions
Zhang, Yitao,Takale, Balaram S.,Gallou, Fabrice,Reilly, John,Lipshutz, Bruce H.
, p. 10556 - 10561 (2019/12/02)
A 1?:?1 Pd?:?ligand complex, [t-BuXPhos(Pd-π-cinnamyl)]OTf, has been identified as a highly robust pre-catalyst for amination reactions leading to diarylamines, where loadings of metal are typically at 1000 ppm Pd, run in water at temperatures between rt and 45 °C. The protocol is exceptionally simple, is readily scaled, and compares very favorably vs. traditional amination conditions. It has also been shown to successfully lead to key intermediates associated with several physiologically active compounds.
4-((2-substituted quinoline-4-yl)amino)benzoyl hydrazine derivatives as well as preparation method and application thereof
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Paragraph 0047; 0050; 0052, (2018/10/26)
The invention relates to 4-((2-substituted quinoline-4-yl)amino)benzoyl hydrazine derivatives as well as a preparation method and application thereof, which relate to N'-substituted methylene-4-((2-substituted quinoline-4-yl)amino)benzoyl hydrazine deriva
Selective non-nucleoside inhibitors of human DNA methyltransferases active in cancer including in cancer stem cells
Valente, Sergio,Liu, Yiwei,Schnekenburger, Michael,Zwergel, Clemens,Cosconati, Sandro,Gros, Christina,Tardugno, Maria,Labella, Donatella,Florean, Cristina,Minden, Steven,Hashimoto, Hideharu,Chang, Yanqi,Zhang, Xing,Kirsch, Gilbert,Novellino, Ettore,Arimondo, Paola B.,Miele, Evelina,Ferretti, Elisabetta,Gulino, Alberto,Diederich, Marc,Cheng, Xiaodong,Mai, Antonello
supporting information, p. 701 - 713 (2014/03/21)
DNA methyltransferases (DNMTs) are important enzymes involved in epigenetic control of gene expression and represent valuable targets in cancer chemotherapy. A number of nucleoside DNMT inhibitors (DNMTi) have been studied in cancer, including in cancer stem cells, and two of them (azacytidine and decitabine) have been approved for treatment of myelodysplastic syndromes. However, only a few non-nucleoside DNMTi have been identified so far, and even fewer have been validated in cancer. Through a process of hit-to-lead optimization, we report here the discovery of compound 5 as a potent non-nucleoside DNMTi that is also selective toward other AdoMet-dependent protein methyltransferases. Compound 5 was potent at single-digit micromolar concentrations against a panel of cancer cells and was less toxic in peripheral blood mononuclear cells than two other compounds tested. In mouse medulloblastoma stem cells, 5 inhibited cell growth, whereas related compound 2 showed high cell differentiation. To the best of our knowledge, 2 and 5 are the first non-nucleoside DNMTi tested in a cancer stem cell line.
Synthetic approaches to DNMT inhibitor SGI-1027 and effects on the U937 leukemia cell line
García-Domínguez, Patricia,Dell'Aversana, Carmela,Alvarez, Rosana,Altucci, Lucia,De Lera, ángel R.
supporting information, p. 1631 - 1635 (2013/04/10)
The known DNMT inhibitor SGI-1027 4 has been synthesized using as key steps Pd-catalyzed Ar-N bond formation reactions performed in a sequential or convergent manner. In the former approach, a by-product, which corresponds to the incorporation of two units of 4-chloroquinoline, was also isolated. The biological effects of compound 4 in the U937 human leukemia cell line are also described.
Auto-tandem catalysis: Synthesis of substituted 11H-indolo [3,2-c]quinolines via palladium-catalyzed intermolecular C-N and intramolecular C-C bond formation
Meyers, Caroline,Rombouts, Geert,Loones, Kristof T. J.,Coelho, Alberto,Maes, Bert U. W.
supporting information; experimental part, p. 465 - 470 (2009/04/10)
D-Ring substituted 11H-indolo[3,2-c]quinolines (4) have been prepared via auto-tandem consecutive intermolecular Buchwald-Hartwig reaction and intramolecular palladium-catalyzed arylation on 4-chloroquinoline (1) with N-unsubstituted 2-chloroanilines (2).
