6345-55-7Relevant articles and documents
Ring closure strategy leads to potent RIPK3 inhibitors
Wu, Shuwei,Xu, Chen,Xia, Kaijiang,Lin, Yu,Tian, Sheng,Ma, Haikuo,Ji, Yuting,Zhu, Fang,He, Sudan,Zhang, Xiaohu
, (2021/03/16)
Necroptosis is a form of regulated necrotic cell death that is independent of caspases. Receptor-interacting protein kinase 3 (RIPK3) has been identified as a key regulator for necroptosis, and has been proposed as a potential therapeutic target for the treatment of diseases associated with necroptosis. In this report, we describe the design, synthesis, and evaluation of a series of novel RIPK3 inhibitors. The lead compound 38 exhibited potent activity (EC50 = 0.42 μM) in blocking TNFα, Smac mimetic and z-VAD (TSZ) induced cell death in HT-29 cells. Mechanistic studies showed that compound 38 bound to RIPK3 with high affinity (Kd = 7.1 nM), and inhibited RIPK3 kinase activity in a ADP-Glo functional assay. In addition, compound 38 displayed good selectivity over another necroptosis regulator RIPK1 (Kd = 6000 nM). Furthermore, compound 38 demonstrated excellent in vitro safety profiles with minimal inhibition of CYP isozymes and hERG potassium channel. Lastly, compound 38 efficiently blocked hypothermia and death in mice in the TNFα-induced systemic inflammatory response syndrome model.
5-nitro-benzothiophene-2-formic acid and chemical synthesis method thereof
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Paragraph 0023-0024, (2021/05/01)
The invention relates to the technical field of benzothiophene compound production, in particular to 5-nitro-benzothiophene-2-formic acid and chemical synthesis method thereof, the method is simple and low in cost, and a solid foundation is provided for mass production and subsequent research of compound materials. The molecular structure of the 5-nitro-benzothiophene-2-formic acid is shown as a formula 1, and meanwhile, the 5-nitro-benzothiophene-2-formic acid has an activity effect of inhibiting oral tooth streptococcus mutans.
Synthesis and biological evaluation of diaryl urea derivatives designed as potential anticarcinoma agents using de novo structure-based lead optimization approach
Azimian, Fereshteh,Dastmalchi, Siavoush,Hamzeh-Mivehroud, Maryam,Hemmati, Salar,Shahbazi Mojarrad, Javid
, (2020/07/13)
To develop inhibitors blocking VEGFR2 and the Raf/MEK/ERK mitogen-activated protein kinase signaling pathway new compounds based on sorafenib were designed, synthesized and biologically evaluated. Using de novo design method, a library of new ligands was