723281-72-9Relevant articles and documents
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.
, p. 1313 - 1319 (2019)
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.
Nitrogen-containing heterocyclic compound and medicinal composition and application thereof
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Paragraph 0295-0300, (2021/05/29)
The invention provides a nitrogen-containing heterocyclic compound with a structure represented by a formula I, or a pharmaceutically acceptable salt, a stereoisomer or a prodrug molecule thereof, and a pharmaceutical composition and application thereof. The compound and the pharmaceutically acceptable salt thereof have an inhibition effect on RIOK2 protease, can effectively inhibit the growth of various tumor cells, and can be used for preparing antitumor drugs.
QUINOLINO-PYRROLIDIN-2-ONE DERIVATIVE AND APPLICATION THEREOF
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Paragraph 0072-0074, (2021/07/08)
Disclosed are a series of quinolino-pyrrolidin-2-one compounds, and application thereof in preparation of drugs for ATM inhibitor-related diseases. The present disclosure specifically relates to a derivative compound represented by formula (I), tautomers thereof or pharmaceutically acceptable compositions thereof.
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.
Development of a Robust Synthesis of Dactolisib on a Commercial Manufacturing Scale
Baenziger, Markus,Pachinger, Werner,Stauffer, Frédéric,Zaugg, Werner
, p. 1908 - 1917 (2019/09/30)
The development of the robust synthesis of 2-methyl-2-[4-[3-methyl-2-oxo-8-(quinolin-3-yl)-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl]-phenyl]propionitrile (dactolisib) on a commercial scale is described. The key step is a Pd-catalyzed Suzuki coupling of 2-[4-(8-bromo-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)-phenyl]-2-methyl-propionitrile to 3-quinoline boronic acid. A special focus is placed on reducing the amount of Pd catalyst used in the Suzuki coupling and purifying the crude drug substance, including removing traces of Pd.
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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, (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.
