A novel series of 2,3-dihydro-[1,4]dioxino[2,3-f]quinazoline derivatives were designed, synthesized and evaluated as reversible and noncovalent epidermal growth factor receptor (EGFR) inhibitors. Most of the compounds exhibited good potency against EGFR^wt and some showed moderate to excellent potency against EGFR^T790M/L858R mutant. The half-maximal inhibitory concentration (IC₅₀) values of twenty-one compounds against EGFR^wt were less than 50 nM, and those of six compounds were less than 10 nM. The IC₅₀ values of eleven compounds against EGFR^T790M/L858R were less than 100 nM. Among these, compound b1 displayed the most potent inhibitory activity against EGFR^wt (IC₅₀ = 2.0 nM) and EGFR^T790M/L858R (IC₅₀ = 6.9 nM). Compounds with excellent inhibitory activities against EGFR^wt and EGFR^T790M/L858R kinase inhibitory activities showed good antiproliferative activities against H358 and A549 cells. Docking study was performed to position compound b1 into the EGFR active pocket to determine the probable binding conformation.

设计，合成和评估了一系列新型的2,3-二氢-[1,4]二恶英[2,3- f ]喹唑啉衍生物，作为可逆的和非共价的表皮生长因子受体（EGFR）抑制剂。大多数化合物对EGFR ^wt表现出良好的效价，而某些对EGFR ^{T790M / L858R}突变体表现出中等至出色的效价。21种化合物对EGFR ^wt的半数最大抑制浓度（IC ₅₀）值小于50 nM，而六种化合物的半数最大抑制浓度（IC ₅₀）小于10 nM。十一种化合物对EGFR ^{T790M / L858R}的IC ₅₀值小于100 nM。其中，化合物b1表现出对EGFR ^wt（IC ₅₀  = 2.0 nM）和EGFR ^{T790M / L858R}（IC ₅₀  = 6.9 nM）的最强抑制活性。对EGFR ^wt和EGFR ^{T790M / L858R}激酶具有出色抑制活性的化合物对H358和A549细胞表现出良好的抗增殖活性。进行了对接研究，将化合物b1置于EGFR活性口袋中，以确定可能的结合构象。