853908-50-6Relevant academic research and scientific papers
Compound serving as Hippo signal channel inhibitor
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, (2020/12/31)
The invention provides a compound represented by a formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. The compound disclosed by the invention has an inhibiting effecton a Hippo signal channel, and can be used for preparing a Hippo signal channel inhibitor. Meanwhile, cell proliferation can be promoted by inhibiting a Hippo signal channel, regeneration of damagedorgans is facilitated, particularly regeneration of damaged liver tissues can be promoted, and acute liver injury can be effectively repaired. Therefore, the compound provided by the invention can also be used for preparing medicines for treating various diseases related to the Hippo signal channel, such as medicines beneficial to regeneration of damaged organs, particularly medicines beneficial to regeneration of damaged liver tissues, and medicines for repairing acute liver injury. The compound can be used for medication research in the field of organ regeneration.
Discovery of 1,8-disubstituted-[1,2,3]triazolo[4,5-c]quinoline derivatives as a new class of Hippo signaling pathway inhibitors
Chen, Pei,Li, L.,Lin, Guifeng,Qiao, Jingxin,Xia, A.,Xiang, Z.,Yang, Shengyong,Zhang, Guo
, (2019/08/12)
Inhibitors of the Hippo signaling pathway have been demonstrated to have a potential clinical application in cases such as tissue repair and organ regeneration. However, there is a lack of potent Hippo pathway inhibitors at present. Herein we report the discovery of a series of 1,8-disubstituted-[1,2,3]triazolo[4,5-c]quinoline derivatives as a new class of Hippo pathway inhibitors by utilizing a cell line-based screening model (A549-CTGF). Structure-activity relationship (SAR) of these compounds was also discussed. The most potent compound in the A549-CTGF cell assay, 11g, was then evaluated by real-time PCR and immunofluorescence assays. Overall, this study provides a starting point for later drug discovery targeting the Hippo signaling pathway.
Discovery of 1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-ones based novel, potent and PI3Kδ selective inhibitors
Bahekar, Rajesh,Dave, Bhushan,Soman, Shubhangi,Patel, Dipam,Chopade, Rajendra,Funde, Radhika,Kumar, Jeevan,Sachchidanand,Giri, Poonam,Chatterjee, Abhijit,Mahapatra, Jogeswar,Vyas, Purvi,Ghoshdastidar, Krishnarup,Bandyopadhyay, Debdutta,Desai, Ranjit C.
supporting information, p. 1313 - 1319 (2019/04/13)
PI3Kδ is implicated in various inflammatory and autoimmune diseases. For the effective treatment of chronic immunological disorders such as rheumatoid arthritis, it is essential to develop isoform selective PI3Kδ inhibitors. Structure guided optimization of an imidazo-quinolinones based pan-PI3K/m-TOR inhibitor (Dactolisib) led to the discovery of a potent and orally bioavailable PI3Kδ isoform selective inhibitor (10h), with an improved efficacy in the animal models.
Design, synthesis and biological evaluation of novel phenylsulfonylurea derivatives as PI3K/mTOR dual inhibitors
Zhao, Bingbing,Lei, Fei,Wang, Caolin,Zhang, Binliang,Yang, Zunhua,Li, Wei,Zhu, Wufu,Xu, Shan
, (2018/07/13)
Five series of novel phenylsulfonylurea derivatives, 19a–d, 20a–d, 21a–d, 22a–d and 23a–d, bearing 4-phenylaminoquinoline scaffold were designed, synthesized and their IC50 values against four cancer cell lines (HepG-2, A549, PC-3 and MCF-7) were evaluated. Most compounds showed moderate cytotoxicity activity against the cancer cell lines. Structure–activity relationships (SARs) and pharmacological results indicated that introduction of 4-aminoquinoline scaffold and phenylsulfonylurea scaffold were beneficial for anti-tumor activity. Moreover, para-methoxyl substitution of 4-anilino moiety and para-halogen substitution of phenylsulfonylurea have different impacts on different series of compounds. Furthermore, the micromolecule group substitution in the 6-position of the quinoline ring have a slight impact on the cellular activity of the target compounds.
Design, synthesis, and antitumor evaluation of quinoline-imidazole derivatives
Xiao, Zhen,Lei, Fei,Chen, Xiuying,Wang, Xiaolei,Cao, Lujie,Ye, Kejun,Zhu, Wufu,Xu, Shan
, (2018/05/14)
A series of compounds bearing quinoline-imidazole (8a–e, 9a–e, 10a–e, 11a–e, and 12a–e) not reported previously were designed and synthesized. The target compounds were evaluated for antitumor activity against A549, PC-3, HepG2, and MCF-7 cells by the MTT method, with NVP-BEZ235 being the positive control. Most compounds showed moderate activity and compound 12a showed the best activity against HepG2, A549, and PC-3 cells, with half-maximal inhibitory concentration (IC50) values of 2.42 ± 1.02 μM, 6.29 ± 0.99 μM, and 5.11 ± 1.00 μM, respectively, which was equal to NVP-BEZ235 (0.54 ± 0.13 μM, 0.36 ± 0.06 μM, 0.20 ± 0.01 μM). Besides, the IC50 value of 12a against the cell line WI-38 (human fetal lung fibroblasts) was 32.8 ± 1.23 μM, indicating that the target compounds were selective for cancer cells. So, 11a and 12a were evaluated against PI3Kα and mTOR to find out if the compounds acted through the PI3K-Akt-mTOR signal transduction pathway. The inhibition ratios to PI3Kα and mTOR were slightly lower than that of NVP-BEZ235, suggesting there may be some other mechanisms of action. The structure–activity relationships and docking study of 11a and 12a revealed that the latter was superior. Moreover, the target compounds showed better in vitro anticancer activity when the C-6 of the quinoline ring was replaced by a bromine atom.
Sulfonylurea compound as well as preparation method and application thereof
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, (2018/09/14)
The invention discloses a sulfonylurea compound, geometrical isomers or pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof, and a preparation method thereof. The sulfonylurea compound, the pharmaceutically acceptable salts, hydrates or solvates serving as active ingredients are mixed with pharmaceutically acceptable carriers or excipients to prepare compositions and preparedinto clinically acceptable dosage forms. The invention further discloses application of the compounds in preparation of medicines for treating and/or preventing proliferative diseases, application inpreparation of medicines for treating and/or preventing cancers, and application in preparation of medicines for treating and/or prostatic cancer, lung cancer and breast cancer.
1H-[1,2,3]triazolo[4,5-c]quinoline derivative, preparation method and uses thereof
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Paragraph 0274; 0275; 0278; 0279, (2018/09/28)
The invention belongs to the field of chemical medicine, particularly relates to a 1H-[1,2,3]triazolo[4,5-c]quinoline derivative, a preparation method and uses thereof, and provides a 1H-[1,2,3]triazolo[4,5-c]quinoline derivative, which has a structure represented by a formula I. The invention further provides a preparation method and uses of the 1H-[1,2,3]triazolo[4,5-c]quinoline derivative. Theformula I is defined in the specification.
Discovery of Potent and Selective Inhibitors of Cdc2-Like Kinase 1 (CLK1) as a New Class of Autophagy Inducers
Sun, Qi-Zheng,Lin, Gui-Feng,Li, Lin-Li,Jin, Xi-Ting,Huang, Lu-Yi,Zhang, Guo,Yang, Wei,Chen, Kai,Xiang, Rong,Chen, Chong,Wei, Yu-Quan,Lu, Guang-Wen,Yang, Sheng-Yong
, p. 6337 - 6352 (2017/08/02)
Autophagy inducers represent new promising agents for the treatment of a wide range of medical illnesses. However, safe autophagy inducers for clinical applications are lacking. Inhibition of cdc2-like kinase 1 (CLK1) was recently found to efficiently induce autophagy. Unfortunately, most of the known CLK1 inhibitors have unsatisfactory selectivity. Herein, we report the discovery of a series of new CLK1 inhibitors containing the 1H-[1,2,3]triazolo[4,5-c]quinoline scaffold. Among them, compound 25 was the most potent and selective, with an IC50 value of 2 nM against CLK1. The crystal structure of CLK1 complexed with compound 25 was solved, and the potency and kinase selectivity of compound 25 were interpreted. Compound 25 was able to induce autophagy in in vitro assays and displayed significant hepatoprotective effects in the acetaminophen (APAP)-induced liver injury mouse model. Collectively, due to its potency and selectivity, compound 25 could be used as a chemical probe or agent in future mechanism-of-action or autophagy-related disease therapy studies.
As the PI3K/mTOR inhibitor compound, its preparation and use
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Paragraph 0189; 0191, (2017/05/20)
The invention discloses a compound used as a PI3K/mTOR inhibitor, which is a compound with a general formula of (IA) or (IB), wherein R1 is selected from hydrogen, halogen, alkyl, alkyloxy, and amido, or forms a fused ring with R2; R2 is selected from hydrogen, amido, sulfamine, sulfonylurea, alkyl, and alkyloxy, or forms a fused ring with R1; R3 is selected from hydrogen, and C1-C6 alkyl; R4 is selected from hydrogen, amido, acylamino, or sulfamine; R5 is selected from hydrogen, halogen, alkyl or alkyloxy. The invention also discloses a preparation method of the compound used as a PI3K/mTOR inhibitor, and an application of the compound as a drug in treating PI3K/mTOR related diseases, especially PI3K/mTOR related cancers.
Combination of mTOR inhibitors and P13-kinase inhibitors, and uses thereof
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, (2016/04/26)
The present invention provides for a method for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject. In yet another aspect, a method of inhibiting phosphorylation of both Akt (S473) and Akt (T308) in a cell is set forth.
