作为表皮生长因子受体抑制剂的新型氨基嘧啶衍生物的设计、合成和生物学评价。

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-03-13 DOI:10.1016/j.bmcl.2025.130188

Huabing Wang , Yule Gui , Shengkai Cui, Xinyi Long, Weizheng Fan, Chunlei Tang

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Design, synthesis, and biological evaluation of novel aminopyrimidine derivatives as EGFR inhibitors

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Design, synthesis, and biological evaluation of novel aminopyrimidine derivatives as EGFR inhibitors

The treatment of non-small cell lung cancer (NSCLC) is significantly challenged by the development of acquired resistance to third-generation epidermal growth factor receptor (EGFR) inhibitors, such as Osimertinib, which limits their therapeutic efficacy. Using the EGFR ^{L858R/T790M/C797S} inhibitor Brigatinib as a reference compound, we designed and synthesized 24 target compounds with aminopyrimidine as the core structure. Among these, the representative compound IIB-5 demonstrated potent inhibition of EGFR^{L858R/T790M/C797S}, achieving an IC₅₀ value of 18.81 nM. It also exhibited strong inhibition against Ba/F3-EGFR^{L858R/T790M/C797S} cells with an IC₅₀ of 97.12 nM, showing a five-fold potency increase over Brigatinib. Compound IIB-5 provides a valuable reference for further research on EGFR inhibitors.

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.