937701-89-8Relevant articles and documents
Facile and efficient synthesis and biological evaluation of 4-anilinoquinazoline derivatives as EGFR inhibitors
Wang, Zheng,Wu, Xue,Wang, Li,Zhang, Jiao,Liu, Jianli,Song, Zhongxing,Tang, Zhishu
, p. 2589 - 2593 (2016/05/09)
Series of 4-anilinoquinazoline derivatives were conveniently and efficiently synthesized and their antitumor activities were evaluated by MTT assay in three human cancer cell lines: H1975, HepG2 and SMMC-7721. New compounds 19a-19h were designed and synthesized to seek for powerful EGFR inhibitors and to explore whether methyl group at C-2 position of quinazoline ring has a positive effect on EGFR inhibition. All the compounds of 19a-19h were found potent against all three cell lines and five compounds (19c, 19d, and 19f-19h) were found more potent against H1975 than gefitinib. SAR studies revealed that methyl group at C-2 position of quinazoline ring could significantly improve the antitumor potency of 4-anilinoquinazolines. The same conclusion was also drawn according to the results of Western blotting analysis. Among all the tested compounds, 19g exhibited extremely potent against H1975 with an IC50 value of 0.11 μM, remarkably lower than that of gefitinib (1.23 μM). The results of western blotting analysis showed that compounds 19c and 19g could notably inhibit the expression of phosphorylated EGFR, especially 19g, almost inhibited completely.
Rhenium and technetium complexes bearing quinazoline derivatives: Progress towards a 99mTc biomarker for EGFR-TK imaging
Fernandes, Celia,Santos, Isabel C.,Santos,Pietzsch, Hans-Jurgen,Kunstler, Jens-Uwe,Kraus, Werner,Rey, Ana,Margaritis, Nikos,Bourkoula, Athanasia,Chiotellis, Aris,Paravatou-Petsotas, Maria,Pirmettis, Ioannis
, p. 3215 - 3225 (2008/12/20)
The quinazoline derivatives (3-chloro-4-fluorophenyl)quinazoline-4,6- diamine (2) and (3-bromophenyl)quinazoline-4,6-diamine (3) were labelled with 99mTc using the "4 + 1" mixed-ligand system [Tc(NS 3)(CN-R)] and the tricarbonyl moiety fac-[Tc(CO)3] +. In the "4 + 1" approach the technetium(iii) is stabilized by a monodentate isocyanide bearing a quinazoline fragment (L 1, L2) and by the tetradentate tripodal ligand tris(2-mercaptoethyl)-amine (NS3). In the "4 + 1" approach, 99mTc-labelling was performed in a two-step procedure, the complexes [Tc(NS3)(L1)] (7a) and [Tc(NS3)(L 2)] (8a) being obtained in about 50-70% yield. In the tricarbonyl approach, the fac-[Tc(CO)3]+ unit is anchored by two different monoanionic chelators bearing the quinazoline derivatives (3-chloro-4-fluorophenyl)quinazoline-4,6-diamine (2) and (3-bromophenyl) quinazoline-4,6-diamine (3). Both chelators have a N2O donor atom set, but one contains a pyrazolyl ring (L5H) and the other contains a pyridine unit (L6H). In both cases the conjugation of the quinazoline to the chelator was done through the secondary amine of the potentially tridentate and monoanionic chelators, the corresponding 99mTc-complexes (10a, 11a) being obtained in quantitative yield. The identities of the 99mTc-labelled quinazolines (7a, 8a, 10a, 11a) were confirmed by comparison with the HPLC profiles of the analogous Re compounds (7, 8, 10, 11). All these Re complexes were characterized by NMR and IR spectroscopy, elemental analysis and in some cases by MS and X-ray diffraction analysis. In vitro studies indicate that the quinazoline fragments, after conjugation to the cyano group (L1, L2) or to the pyrazolyl containing chelator (L5H), as well as the corresponding Re complexes (7, 8, 10) inhibit significantly the EGFR autophosphorylation and also inhibit A431 cell growth. These two effects were also found for the pyridine-containing chelator (L6H) and corresponding Re complex (11), although to a lesser extent. The Royal Society of Chemistry 2008.
