92000-89-0Relevant academic research and scientific papers
Synthesis and biological evaluation of quinazoline derivatives – A SAR study of novel inhibitors of ABCG2
Krapf, Michael K.,Gallus, Jennifer,Spindler, Anna,Wiese, Michael
, p. 506 - 525 (2018/11/06)
Multidrug resistance (MDR) is a major obstacle for effective chemotherapeutic treatment of cancer frequently leading to failure of the therapy. MDR is often associated with the overexpression of ABC transport proteins like ABCB1 or ABCG2 which efflux harmful substances out of cells at the cost of ATP hydrolysis. One way to overcome MDR is to apply potent inhibitors of ABC transporters to restore the sensitivity of the cells toward cytostatic agents. This study focusses on the synthesis and evaluation of novel 2,4-disubstituted quinazoline derivatives regarding the structure-activity-relationship (SAR), their ability to reverse MDR and their mode of interaction with ABCG2. Hence, the inhibitory potency and selectivity toward ABCG2 was determined. Moreover, the intrinsic cytotoxicity and the reversal of MDR were investigated. Interaction type studies with the substrate Hoechst 33342 and conformational analyses of ABCG2 with 5D3 monoclonal antibody were performed for a better understanding of the underlying mechanisms. In our study we could further enhance the inhibitory effect against ABCG2 (compound 31, IC50: 55 nM) and identify the structural features that are crucial for inhibitory potency, the impact on transport activity and binding to the protein.
2,4,6-Substituted Quinazolines with Extraordinary Inhibitory Potency toward ABCG2
Krapf, Michael K.,Gallus, Jennifer,Namasivayam, Vigneshwaran,Wiese, Michael
, p. 7952 - 7976 (2018/09/06)
Several members of the ABC transporter superfamily play a decisive role in the development of multidrug resistance (MDR) in cancer. One of these MDR associated efflux transporters is ABCG2. One way to overcome this MDR is the coadministration of potent in
Synthesis and Biological Evaluation of 4-Anilino-quinazolines and -quinolines as Inhibitors of Breast Cancer Resistance Protein (ABCG2)
Krapf, Michael K.,Wiese, Michael
, p. 5449 - 5461 (2016/07/06)
Chemotherapeutic treatment of cancer often fails due to overexpression of the ATP-binding cassette (ABC) transport proteins, like ABCG2, triggering active efflux of various structurally unrelated drugs. This so-called multidrug resistance (MDR) may be rev
Triazines and Related Products. Part 27. Thermolysis of 4-Anilino-1,2,3-benzotriazines
Baig, Ghouse Unissa,Stevens, Malcolm F. G.,Vaughan, Keith
, p. 999 - 1003 (2007/10/02)
Thermolysis of 4-(4-cyanoanilino)-1,2,3-benzotriazine (1a) in morpholine affords 3--4-(4-cyanophenylimino)-3,4-dihydro-1,2,3-benzotriazole (3a) in addition to the major product 2-amino-N2-(4-cyanophenyl)-N
