- Synthesis and in vitro anti-bladder cancer activity evaluation of quinazolinyl-arylurea derivatives
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Based on the structural modification of molecular-targeted agent sorafenib, a series of quinazolinyl-arylurea derivatives were synthesized and evaluated for their anti-proliferative activities against six human cancer cell lines. Compared with other cell lines tested, T24 was more sensitive to most compounds. Compound 7j exhibited the best profile with lower IC50 value and favorable selectivity. In this study, we focused on 7j-induced death forms of T24 cells and tried to elucidate the reason for its potent proliferative inhibitory activity. Compound 7j treatment could trigger three different cell death forms including apoptosis, ferroptosis, and autophagy; which form would occur depended on the concentrations and incubation time of 7j: (1) Lower concentrations within the initial 8 h of 7j treatment led to apoptosis-dependent death. (2) Ferroptosis and autophagy occurred in the case of higher concentrations combining with extended incubation time through effectively regulating the Sxc?/GPx4/ROS and PI3K/Akt/mTOR/ULK1 pathways, respectively. (3) The above death forms were closely associated with intracellular ROS generation and decreased mitochondrial membrane potential induced by 7j. In molecular docking and structure-activity relationship analyses, 7j could bind well to the active site of the corresponding receptor glutathione peroxidase 4 (GPx4). Compound 7j could be a promising lead for molecular-targeted anti-bladder cancer agents’ discovery.
- Chen, Jia-Nian,Li, Ting,Cheng, Li,Qin, Tai-Sheng,Sun, Ye-Xiang,Chen, Chu-Ting,He, Yue-Zhen,Liu, Guang,Yao, Di,Wei, Ying,Li, Qiu-Yin,Zhang, Guang-Ji
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- N - (4 - (3 - amino - 1 H - indazole - 4 - yl) phenyl) - N' - (2 - fluoro - 5 - methylphenyl) urea intermediate preparation method
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The invention provides a preparation method of N-(4-(3-amino-1H-indazol-4-yl) phenyl)-N'-(2-fluoro-5-methylphenyl) urea and an intermediate thereof. Specifically, the invention provides a preparation method of a borate ester compound as shown in a formula I, and the preparation method comprises the following steps: enabling a compound as shown in a formula III to react with a compound as shown in a formula IV to generate a compound as shown in a formula V, and enabling the compound as shown in the formula V to react with a boron reagent to generate the compound as shown in the formula I. The method has the characteristics of convenience in reaction, easiness in obtainment of the intermediate, high yield, high product purity of above 98.5%, low cost of raw materials and the like, and is suitable for industrial application.
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Paragraph 0120; 0122; 0123
(2018/03/02)
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- With anti-tumor effect of a quinazoline-urea derivative and its application (by machine translation)
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The present invention relates to a of the general formula (II) anti-tumor function of said quinazoline-urea derivative and its application. The definition of the substituent in the general formula (II) in the specification. This invention, in order to SUO draw non-Buddhist nun and Geftinat compounds as the precursor, retention of SUO draw non-Buddhist nun the pharmocology-carbamido; at the same time, such as in reserved [...] EGFR-TKIs Geftinat, synthesis, and obtain a series of quinazoline-urea derivatives, by the in vitro activity tests, some compounds exhibit excellent anti-tumor activity, such derivatives have high research and utility value. (II). (by machine translation)
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Paragraph 0139-0142; 0166
(2016/11/02)
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- A simple and efficient synthesis of diaryl ureas with reduction of the intermediate isocyanate by triethylamine
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Thirty symmetrical diaryl urea derivatives were synthesised in moderate to excellent yields from arylamine and triphosgene with triethylamine as a reducing agent for the intermediate, isocyanate. It was significant that part of the products could be collected in almost quantitative yield without column chromatography. The procedure under mild reaction conditions was tolerant of a wide range of functional groups. The structures of the compounds were determined by NMR, MS and X-ray crystallographic analyses.
- Zhou, Shuguang,Yao, Ting,Yi, Jicheng,Li, Dashuai,Xiong, Jing
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p. 315 - 319
(2013/07/27)
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- A new class of inhibitors of secretory phospholipase A2: enolized 1,3-dioxane-4,6-dione-5-carboxamides
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Enolized 1,3-dioxane-4,6-dione-5-carboxamides a were identified as a new class of inhibitors of secretory phospholipase A2 from human polymorphonuclear leucocytes (h-PMN PLA2).Among the more than 30 compounds synthesized, the most potent inhibitors (IC50 0.6-10 μM) were found in the series of 2,4-disubstituted phenyl analogues of a.Compound 1a was selected for evaluation of its biological profile.This substance potently inhibited secretory PLA2s from several sources other than human PMNs, with a clear preference for group II over group I PLA2, whereas humancytosolic PLA2 and phospholipase C were not significantly affected.Inhibition of h-PMN PLA2 was calcium-dependent.In intact mammalian cells stimulated in vitro, the release of arachidonic acid and the generation of prostaglandins and leukotrienes were inhibited at concentrations compatible with inhibition of PLA2 as an underlying mechanism.In animal models in vivo (carragheenan oedema, adjuvant arthritis, pertussis pleurisy) 1a showed antiinflammatory activity, although the effect was rather weak compared with standard reference compounds. secretory human PMN phospholipase A2 / enolized 1,3-dioxane-4,6-dione-5-carboxamide inhibitors / cellular eicosanoid synthesis / in vivo antiinflammatory activity / molecular modelling / structure-activity relationship
- Breitenstein, W.,Maerki, F.,Roggo, S.,Wiesenberg, I,Pfeilschifter, J.,et al.
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p. 649 - 658
(2007/10/02)
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