402855-06-5Relevant articles and documents
6-Oxooxazolidine–quinazolines as noncovalent inhibitors with the potential to target mutant forms of EGFR
Shao, Jiaan,Chen, En,Shu, Ke,Chen, Wenteng,Zhang, Guolin,Yu, Yongping
, p. 3359 - 3370 (2016)
Despite the remarkable benefits of gefitinib, the clinical efficacy is eventually diminished due to the acquired point mutations in the EGFR (T790M). To address this unmet medical need, we demonstrated a strategy to prepare a hybrid analogue consisting of the oxooxazolidine ring and the quinazoline scaffold and provided alternative noncovalent inhibitors targeting mutant forms of EGFR. Most of the derivatives displayed moderate to good anti-proliferative activity against gefitinib-resistant NCI-H1975. Some of them exhibited potent EGFR kinase inhibitory activities, especially on EGFRT790Mand EGFRL858Rkinases. SAR studies led to the identification of a hit 9a that can target both of the most common EGFR mutants: L858R and T790M. Also, 9a displayed weaker inhibitory against cancer cell lines with low level of EGFR expression and good chemical stability under different pH conditions. The work presented herein showed the potential for developing noncovalent inhibitors targeting EGFR mutants.
QUINAZOLINE DERIVATIVE AND PREPARATION METHOD THEREFOR
-
Paragraph 0100; 0191, (2016/08/17)
The present invention relates to a quinazoline derivative shown in formula (I) and a preparation method therefor, a pharmaceutical composition comprising the compound shown in formula (I), and an application of the compound in preparing drugs for curing and preventing tumors. The compound of the present invention can irreversibly prevent EGFR phosphorylation, and effectively depress signal transduction of cancer cells, and accordingly has higher anti-tumor activity in vitro and in vivo,
AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE THEREOF
-
Paragraph 00210-00211, (2014/11/13)
Provided herein are aminoquinazoline compounds, salts and uses thereof. The compounds have Formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug ther
