677748-48-0Relevant articles and documents
Design, synthesis and molecular modeling studies of 2-styrylquinazoline derivatives as EGFR inhibitors and apoptosis inducers
Amin, Noha H.,Elsaadi, Mohammed T.,Zaki, Shimaa S.,Abdel-Rahman, Hamdy M.
, (2020)
Herein, we report the synthesis of novel 2-substituted styrylquinazolines conjugated with aniline or sulfonamide moieties, anticipated to act as potent anticancer therapeutic agents through preferential EGFR inhibition. In doing so, all the synthesized compounds were screened for their in vitro anticancer activities (nine subpanels) at the National Cancer Institute (NCI), USA. The resulting two most active anticancer compounds (7b and 8c) were then chemically manipulated to investigate feasible derivatives (12a-e and 15a-d). MTT cytotoxicity, in vitro cell free EGFR and anti-proliferative activity against EGFR/ A549 cell line evaluation for the most active broadly spectrum candidates (7a/b, 8c/e, 12b and 15d) was conducted. Promising results were obtained for the styrylquinazoline-benzenesulfonamide derivative 8c (IC50 = 8.62 μM, 0.190 μM and = 79.25%), if compared to lapatanib (IC50 = 11.98 μM, 0.190 μM, and 79.25%), respectively. Moreover, its apoptotic induction potential was studied through cell cycle analysis, Annexin-V and caspase-3 activation assays. Results showed a clear cell arrest at G2/M phase, a late apoptotic increase (76 folds) and a fruitful caspase-3 expression change (8 folds), compared to the control. Finally, molecular docking studies of compounds 7a/b, 8c/e, 12b and 15d revealed proper fitting into the active site of EGFR with a low binding energy score for compound 8c (?13.19 Kcal/mole), compared to lapatanib (?14.54 Kcal/mole).
A new DMAP-catalyzed and microwave-assisted approach for introducing heteroarylamino substituents at position-4 of the quinazoline ring
Gellis, Armand,Kieffer, Charline,Primas, Nicolas,Lanzada, Gilles,Giorgi, Michel,Verhaeghe, Pierre,Vanelle, Patrice
, p. 8257 - 8266 (2015/03/03)
We report herein a new methodology for synthesizing quinazoline derivatives bearing a heteroarylamino moiety at position-4 of the quinazoline ring. As an alternative to the Buchwald-Hartwig cross-coupling reaction, which appears, until now, as the only efficient way to react 4-chloroquinazolines with numerous amino nitrogen-containing heterocycles displaying poor nucleophilicity, we developed a DMAP-catalyzed reaction involving microwave irradiation. Optimization of the reaction conditions led to the use of 30 mol % of DMAP in toluene, using a monomode microwave reactor and sealed vials. Moreover, the SNAr reaction intermediate salt was isolated and fully characterized. Finally, the procedure was extended to two different 2-substituted-quinazoline series and also to various anilines, demonstrating that this approach was a general efficient way to access to such 4-substituted quinazoline scaffolds of high pharmaceutical interest.
Synthesis of substituted quinazolines: Application to the synthesis of verubulin
Lockman, Jeffrey W.,Klimova, Yevgeniya,Anderson, Mark B.,Willardsen, J. Adam
experimental part, p. 1715 - 1723 (2012/04/10)
Through newly adapted methodology, 2-methyl-3H-quinazolin-4-one was activated using a number of methods followed by displacement to afford 4-aminoquinazolines. The most useful of these processes utilize the p-toluenesulfonate ester or I2/PPh3 activation. Using this methodology, the anticancer vascular targeting clinical candidate verubulin (1) was synthesized in a highly efficient manner. Copyright Taylor & Francis Group, LLC.
