853908-50-6Relevant articles and documents
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 1,3-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 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.
