169205-77-0Relevant articles and documents
Microwave-assisted synthesis of new 6-ureido-4-anilinoquinazoline derivatives
Zheng, Youguang,Gao, Caiyun,Huang, Rongrong,Liu, Yi,Xue, Yunsheng,An, Lin
, p. 95 - 98 (2016)
An efficient rapid method for the synthesis of new 6-ureido-4-anilinoquinazoline derivatives derived from 2-amino-5-nitrobenzoic acid under microwave irradiation has been developed. All of the new compounds were identified by 1H NMR, 13C NMR, IR, MS and elemental analyses.
4-Anilinoquinazolines with Lavendustin A subunit as inhibitors of epidermal growth factor receptor tyrosine kinase: Syntheses, chemical and pharmacological properties
Albuschat, Rica,L?we, Werner,Weber, Manuela,Luger, Peter,Jendrossek, Verena
, p. 1001 - 1011 (2004)
4-Anilinoquinazoline derivatives are widely investigated due to their potent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitory activity. Two 4-anilinoquinazolines with Lavendustin A subunit (10a,b) were synthesized and examined for their EGFR tyrosine kinase inhibitory activity as well as their antiproliferative properties on variant human cancer cell lines. Both compounds maintained their EGFR tyrosine kinase inhibitory activity at the 10-7:M level and led to significant growth inhibition in certain leukemia, non-small cell lung cancer (NSCLC), ovarian cancer, renal cancer and breast cancer cell lines with GI50 values at the 10-6 M level. There could not be observed any notable difference between 10a and 10b regarding to their antiproliferative activity. Interestingly, we observed the high tendency of 10a and 10b to include certain solvents, e.g. water, DMF, DMSO, which may be due to the remarkable number of hydrogen accepting/donating groups in 10a and b. An X-ray analysis of 10a including water and DMF illustrates a possible hydrogen bond pattern and could serve as information for preferred receptor (e.g. EGFR tyrosine kinase) binding sites. Finally, we aimed for irreversible EGFR tyrosine kinase inhibitors. The p-quinone derivatives 11a and 11b, which contain a Michael acceptor position according to the irreversible inhibitor CI-1033, could be derived from the p-hydroquinone derivatives 10a or 10b, respectively, by oxidation. However, due to their instability 11a and 11b could not be obtained in a pure form.
Design, synthesis and biological evaluation of cinnamamide-quinazoline derivatives as potential EGFR inhibitors to reverse T790M mutation
Zhang, Bin,Xu, Zichen,Liu, Qingqing,Xia, Shengjin,Liu, Zhikun,Liao, Zhixin,Gou, Shaohua
, (2021/10/16)
Gatekeeper T790M mutation in EGFR is the most common factor for acquired resistance. Acrylamide-bearing 4-anilinoquinazoline scaffold are powerful irreversible inhibitors for overcoming resistance. In this work, three series of EGFR inhibitors derived from incorporation of cinnamamide into the quinazoline scaffold were designed and synthesized to reverse resistance resulting from insurgence of T790M mutation. SAR studies revealed that methoxy and acetoxy substitutions on the cinnamic phenyl ring were found to elevate the activity. In particular, compound 7g emerged as the most potent derivative against mutant-type H1975 cells, which exhibited comparable activity to osimertinib (0.95 μM) towards H1975 cells with an IC50 value of 1.22 μM. Kinase inhibition studies indicated that 7g showed excellent inhibitory effect on EGFRT790M enzyme, which was 11 times more effective than gefitinib. Besides, selectivity index of 7g toward the EGFRT790M mutant over the EGFRWT is 2.72, hinting its effect of reducing off-target. Mechanism study indicated that 7g induced apoptosis of H1975 cells and arrest the cell cycle at G2/M phase in a dose-dependent manner. Moreover, 7g could significantly inhibit the expression of p-EGFR and its downstream p-AKT and p-ERK in H1975 cells. Molecular docking was also performed to gain insights into the ligand-binding interactions of 7g inside EGFRWT and EGFRT790M binding sites.
A THERANOSTIC PROBE AND ITS USE FOR TARGETING AND/OR LABELING THE EGFR KINASE AND/OR THE CELLS EXPRESSING EGFR OR ITS FAMILY MEMBERS
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Page/Page column 12-13; 16, (2020/09/08)
The present application is directed to a theranostic probe and its use for targeting and/or labeling the EGFR kinase and/or the cells expressing EGFR or its family members.
Novel series of 6-(2-substitutedacetamido)-4-anilinoquinazolines as EGFR-ERK signal transduction inhibitors in MCF-7 breast cancer cells
Ismail, Rania S.M.,Abou-Seri, Sahar M.,Eldehna, Wagdy M.,Ismail, Nasser S.M.,Elgazwi, Sara M.,Ghabbour, Hazem A.,Ahmed, Mahmoud Salama,Halaweish, Fathi T.,Abou El Ella, Dalal A.
supporting information, p. 782 - 796 (2018/06/29)
Epidermal growth factor receptor (EGFR) signaling pathway has been previously investigated for its significant role in the progression of different types of malignant tumors, where development of small molecules targeting EGFR is well known strategy for design of antitumor agents. Herein, we report the design and synthesis of two series of 6-(2-substitutedacetamido)-4-anilinoquinazolines (6a-x and 13a-d) as EGFR inhibitors. All the newly synthesized quinazoline derivatives were in vitro evaluated for their anti-proliferative activity towards MCF-7 (Breast Cancer) and HepG2 (Hepatocellular carcinoma) cell lines. In particular, compound 6n showed significant inhibitory activity against MCF-7 and HepG2 cell lines (IC50 = 3 and 16 μM, respectively), compared to that of Erlotinib (IC50 = 20 and 25 μM, respectively). Western blotting of 6n at MCF-7 cell line revealed the dual inhibitory activity of 6n towards diminishing the phosphorylated levels for EGFR and ERK. Also, ELISA assay confirmed the anti-EGFR activity of compound 6n (IC50 = 0.037 μM). Finally, a molecular docking study showed the potential binding mode of 6n within the ATP catalytic binding site of EGFR, exhibiting similar binding mode to EGFR inhibitor Erlotinib.
