6590-94-9Relevant academic research and scientific papers
COMPOUNDS WITH COPPER- OR ZINC-ACTIVATED TOXICITY AGAINST MICROBIAL INFECTION
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, (2022/02/05)
Heterocyclic compounds with a novel pyrazole thioamide-based NNSN structural motif, having highly effective zinc- or copper-activated toxicity against microbial infections at micromolar or nanomolar minimum inhibitory concentrations (MIC), and methods of making and using same.
Design, synthesis and biological evaluation of novel 2,4-disubstituted quinazoline derivatives targeting H1975 cells via EGFR-PI3K signaling pathway
Chao, Gao,Dai, Honglin,Ke, Yu,Li, Erdong,Lihong, Shan,Liu, Hongmin,Liu, Limin,Si, Xiaojie,Wang, Zhengjie,Yang, Zhang,Zhang, Luye,Zhang, Qiurong,Zheng, Jiaxin
, (2021/07/28)
In order to find new and highly effective anti-tumor drugs with targeted therapeutic effects, a series of novel 4-aminoquinazoline derivatives containing N-phenylacetamide structure were designed, synthesized and evaluated for antitumor activity against four human cancer cell lines (H1975, PC-3, MDA-MB-231 and MGC-803) using MTT assay. The results showed that the compound 19e had the most potent antiproliferative activity against H1975, PC-3, MDA-MB-231 and MGC-803 cell lines. At the same time, compound 19e could significantly inhibit the colony formation and migration of H1975 cells. Compound 19e also arrested the H1975 cell cycle in the G1 phase and mediated cell apoptosis, promoted the accumulation of ROS in H1975 cells. Furthermore, compound 19e exerted antitumor effect in vitro by reducing the expression of anti-apoptotic protein Bcl-2 and increasing the pro-apoptotic protein Bax and p53. Mechanistically, compound 19e could significantly decreased the phosphorylation of EGFR and its downstream protein PI3K in H1975 cells. Which indicated that compound 19e targeted H1975 cell via interfering with EGFR-PI3K signaling pathway. Molecular docking showed that compound 19e could bind into the active pocket of EGFR. Those work suggested that compound 19e would have remarkable implications for further design of anti-tumor agents.
A catalyst-free method for the synthesis of 1,4,2-dithiazoles from isothiocyanates and hydroxylamine triflic acid salts
An, Zhenyu,Liu, Yafeng,Ren, Yi,Wang, Ting,Yan, Rulong
supporting information, p. 6206 - 6209 (2021/07/28)
A catalyst-free method for the preparation of 1,4,2-dithiazoles is developed by reactions of isothiocyanates with hydroxylamine triflic acid salts. This reaction achieves C-S, C-N, and S-N bond formation, and a range of products are obtained in moderate to good yields. The obvious feature is using shelf-stable hydroxylamine triflic acid salts as a N source to synthesize heterocycles under mild conditions.
Synthesis and biological evaluation of innovative thiourea derivatives as PHGDH inhibitors
Xiang, Jiawei,Tao, Lei,Zhou, Yue,Tan, Yuping,Li, Zicheng,Zhao, Yinglan,Sun, Qingxiang,Luo, Youfu
, p. 3873 - 3886 (2020/05/29)
In order to discover novel compounds with inhibitory activity against 3-phosphoglycerate dehydrogenase (PHGDH), a series of thiourea derivatives were designed and synthesized based on the structural modification of compound 5d. Compound 5d emerged from the visual database of ChemDiv of 200,000 small molecules by docking score ranking. Inhibition experiments on PHGDH activity of newly synthesized compounds were performed in vitro. Compounds with more than 30percent inhibitory rate at 25?μM on PHGDH were screened for IC50 measurement. Anti-proliferative activity of 4a, 5a, 6e, 6n against A2780, MDA-MB-468, MDA-MB-231 and HEK293T in vitro was evaluated. The results showed that the compound 4a displayed the best inhibitory activity on PHGDH among the newly synthesized compounds, and the compounds 4a, 5a, 6n had a better proliferation inhibition effect on human A2780 cell line than NCT-503 reported previously. In addition, 2D interaction diagrams revealed potential action modes of active compounds with PHGDH.
Pyrazolone amide antifungal drug, and preparation method and application thereof
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Paragraph 0099; 0100; 0102; 0103, (2018/09/12)
The invention discloses a pyrazolone amide antifungal drug or its pharmaceutically acceptable salt. The structure of the compound is represented by general formula I shown in the description. In the general formula I, X is O or S; R1 is hydrogen, or a monosubstituent or a polysubstituent positioned at any position of a phenyl ring; R2 is hydrogen, a substituted or unsubstituted aromatic ring or cycloaliphatic ring, or a lower acyl group; and one of R3 and R4 is an amino group, and the remaining one is carbonyl oxygen. The invention discloses a preparation method of the compound, and an application of the compound in the preparation of an antifungal drug. Results of in-vitro antifungal activity experiments show that most of the compounds represented by general formula show have good antifungal activity characteristics, and have better antifungal activity on fungi comprising Candida albicans, fluconazole-resistant Candida albicans, Cryptococcus neoformans and Candida glabrata than a positive drug fluconazole.
ANTIFUNGAL COMPOUNDS AND USES THEREOF
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Paragraph 00246, (2017/09/08)
Provided herein are compounds (e.g., compounds of Formulae (I), (II), and (III)) which are anti-fungal agents and can be used in the treatment of diseases, including infectious diseases. The invention provides methods of treating diseases in a subject (e.g., infectious diseases such as fungal infections), and methods of killing or inhibiting the growth of fungi in or on a subject or biological sample. The compounds may be used in subjects, in clinical settings, or in agricultural settings.
Discovery of novel anti-angiogenesis agents. Part 6: Multi-targeted RTK inhibitors
Zhang, Lin,Shan, Yuanyuan,Li, Chuansheng,Sun, Ying,Su, Ping,Wang, Jinfeng,Li, Lisha,Pan, Xiaoyan,Zhang, Jie
, p. 275 - 285 (2017/01/10)
Angiogenesis is modulated by a multitude of pro-angiogenic factors including VEGFR-2, Tie-2, and EphB4. Moreover, their crosstalk also had been well elaborated. We have identified several diarylurea-based VEGFR-2 inhibitors as potential anti-angiogenesis agents. As a continuation to our previous research, two series of diaryl malonamide and diaryl thiourea derivatives have been developed as multiplex VEGFR-2/Tie-2/EphB4 inhibitors. Interestingly, the biological evaluation indicated that several compounds bearing trifluoromethyl or trifluoromethoxyl exhibited promising multiplex inhibition against angiogenesis-related VEGFR-2, Tie-2, and EphB4. The representative compound (18a) displayed both potent multi-targeted RTK inhibition and considerable antiproliferative activities against human umbilical vein endothelial cells (EA.hy926). These results will contribute to the discovery of novel muti-targeted anti-angiogenesis agents.
Discovery of novel anti-angiogenesis agents. Part 8: Diaryl thiourea bearing 1H-indazole-3-amine as multi-target RTKs inhibitors
Sun, Ying,Shan, Yuanyuan,Li, Chuansheng,Si, Ru,Pan, Xiaoyan,Wang, Binghe,Zhang, Jie
, p. 373 - 385 (2017/10/16)
VEGFR-2, TIE-2, and EphB4 are essential for both angiogenesis and tumorigenesis. Herein, we designed and prepared three classes of multi-target inhibitors based on the extensive sequence homology along the kinase domain of angiogenic RTKs. Biological evaluation indicated that these multi-target inhibitors exhibited considerable potential as novel anti-angiogeneic and anticancer agents. Among them, a diaryl thiourea bearing 1H-indazole-3-amine (16a) displayed the most potent RTK inhibition and excellent selectivity. It also showed inhibition on viability of human umbilical vein endothelial cells and anti-proliferation against a broad spectrum of cancer cells. Therefore, 1H-indazole-3-amine could serve as a promising hinge binding group for multi-target inhibitors of VEGFR-2, Tie-2, and EphB4.
Synthesis and biological evaluation of terminal functionalized thiourea-containing dipeptides as antitumor agents
Huang, Ri-Zhen,Zhang, Bin,Huang, Xiao-Chao,Liang, Gui-Bin,Qin, Jian-Mei,Pan, Ying-Ming,Liao, Zhi-Xin,Wang, Heng-Shan
, p. 8866 - 8878 (2017/02/10)
A series of antitumor agents based on terminal functionalized dipeptide derivatives containing the thiourea moiety were synthesized and evaluated for antiproliferative activity using a panel of cancer cell lines, and the effects and mechanism of apoptosis induction were determined. These compounds exhibited significant selectivity to different cancer cell lines with IC50 values at micromolar concentrations. In particular, compound I-11 appeared to be the most potent compound, with an IC50 = 4.85 ± 1.44 μM against the NCI-H460 cell line, at least partly, by the induction of apoptosis. Mechanistically, compound I-11 induced the activation of caspase-12 and CHOP, which triggered apoptotic signalling via the ROS-dependent endoplasmic reticulum pathway and arrested the cell cycle at the S phase. Thus, we concluded that dipeptide derivatives containing the thiourea moiety terminally functionalized by electron-withdrawing substituents may be potential antitumor agents for further investigation.
Diarylthiourea compound with antitumor activity, and preparation method and application thereof
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Paragraph 0056; 0057; 0088; 0089, (2017/02/02)
The invention provides a diarylthiourea compound with antitumor activity, and a preparation method and application thereof. The compound has a structural formula as described in the specification. In the structural formula, R1 and R2 are selected from the group consisting of a halogen group or a group formed by R1 and R2 together; and Ar is a nitrogen heterocyclic ring of pyridine, indazole or quinazoline. The compound provided by the invention has good inhibitory activity to VEGFR-2 kinase, so a signal channel induced by the VEGFR-2 kinase can be blocked through inhibition of the activity of the VEGFR-2 kinase, and proliferation and migration of tumor cells are inhibited; thus, the compound can be applied in preparation of antitumor drugs. Meanwhile, the preparation method for the compound has the following advantages: raw materials are easily available; reaction conditions are mild; the process of reaction is simple to operate; and used reagents are cheap.
