327-78-6Relevant articles and documents
Discovery of Potent EGFR Inhibitors With 6-Arylureido-4-anilinoquinazoline Derivatives
Li, Meng,Xue, Na,Liu, Xingang,Wang, Qiaoyun,Yan, Hongyi,Liu, Yifan,Wang, Lei,Shi, Xiaowei,Cao, Deying,Zhang, Kai,Zhang, Yang
, (2021/06/14)
According to the classical pharmacophore fusion strategy, a series of 6-arylureido-4-anilinoquinazoline derivatives (Compounds 7a–t) were designed, synthesized, and biologically evaluated by the standard CCK-8 method and enzyme inhibition assay. Among the title compounds, Compounds 7a, 7c, 7d, 7f, 7i, 7o, 7p, and 7q exhibited promising anti-proliferative bioactivities, especially Compound 7i, which had excellent antitumor activity against the A549, HT-29, and MCF-7 cell lines (IC50 = 2.25, 1.72, and 2.81?μM, respectively) compared with gefitinib, erlotinib, and sorafenib. In addition, the enzyme activity inhibition assay indicated that the synthesized compounds had sub-micromolar inhibitory levels (IC50, 11.66–867.1?nM), which was consistent with the results of the tumor cell line growth inhibition tests. By comparing the binding mechanisms of Compound 7i (17.32?nM), gefitinib (25.42?nM), and erlotinib (33.25?nM) to the EGFR, it was found that Compound 7i could extend into the effective region with a similar action conformation to that of gefitinib and interact with residues L85, D86, and R127, increasing the binding affinity of Compound 7i to the EGFR. Based on the molecular hybridization strategy, 14 compounds with EGFR inhibitory activity were designed and synthesized, and the action mechanism was explored through computational approaches, providing valuable clues for the research of antitumor agents based on EGFR inhibitors.
POLYAROMATIC UREA DERIVATIVES AND THEIR USE IN THE TREATMENT OF MUSCLE DISEASES
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Page/Page column 118, (2021/01/29)
The current invention provides urea derivatives, in particular compounds having the core structure heteroaryl-NH-CO-NH-aryl-O- heteroaryl, for use in treating, ameliorating, delaying, curing and/ or preventing a disease or condition associated with muscle cells and/or satellite cells, such as Duchenne muscular dystrophy, Becker muscular dystrophy, cachexia or sarcopenia.
Synthesis, anticancer activity, and β-lactoglobulin binding interactions of multitargeted kinase inhibitor sorafenib tosylate (SORt) using spectroscopic and molecular modelling approaches
Tanzadehpanah, Hamid,Bahmani, Asrin,Hosseinpour Moghadam, Neda,Gholami, Hamid,Mahaki, Hanie,Farmany, Abbas,Saidijam, Massoud
, p. 117 - 128 (2020/08/19)
Sorafenib tosylate (SORt) is an oral multikinase inhibitor used for treatment of advanced renal cell, liver, and thyroid cancers. In this study, this drug was synthesized and its antiproliferative activities against HCT116 and CT26 cells were assessed. The interaction of SORt with β-lactoglobulin (BLG) was studied using different fluorescence techniques, circular dichroism (CD), zeta potential measurements, and docking simulation. The results of infrared (IR), mass, HNMR, and CNMR spectra demonstrated that the drug was produced with high quality, purity, and efficiency. SORt showed potent cytotoxicity against HCT116 and CT26 cells with IC50 of 8.12 and 5.42 μM, respectively. For BLG binding of SORt, the results showed that static quenching was the cause of the high affinity drug–protein interaction. Three-dimensional fluorescence and synchronous spectra indicated that SORt conformation was changed at different levels. CD suggested that the α-helix content remained almost constant in the BLG–SORt complex, whereas random coil content decreased. Zeta potential values of BLG were more positive after binding with SORt, due to electrostatic interactions between BLG and SORt. Thermodynamic parameters confirmed van der Waals and hydrogen bond interactions in the complex formation. Molecular modelling predicted the presence of hydrogen bonds and electrostatic forces in the BLG–SORt system, which was consistent with the experimental results.