267243-68-5Relevant articles and documents
Quinazoline derivative, preparation method and pharmaceutical application thereof
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, (2020/04/17)
The invention discloses a quinazoline derivative, a preparation method and pharmaceutical application thereof. The invention provides the quinazoline derivative which is a compound shown as formula Iin the specification, and also provides a pharmaceutical
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 (2016/07/20)
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.
Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase
Hur, Wooyoung,Velentza, Anastasia,Kim, Sungjoon,Flatauer, Laura,Jiang, Xinnong,Valente, David,Mason, Daniel E.,Suzuki, Melissa,Larson, Brad,Zhang, Jianming,Zagorska, Anna,DiDonato, Michael,Nagle, Advait,Warmuth, Markus,Balk, Steven P.,Peters, Eric C.,Gray, Nathanael S.
supporting information; experimental part, p. 5916 - 5919 (2009/06/25)
Irreversible HER/erbB inhibitors selectively inhibit HER-family kinases by targeting a unique cysteine residue located within the ATP-binding pocket. Sequence alignment reveals that this rare cysteine is also present in ten other protein kinases including all five Tec-family members. We demonstrate that the Tec-family kinase Bmx is potently inhibited by irreversible modification at Cys496 by clinical stage EGFR inhibitors such as CI-1033. This cross-reactivity may have significant clinical implications.