中文摘要：

为深究WZ系列抑制剂强效抑制突变型表皮生长因子受体（T790MEGFR）的内在机制，用密度泛函理论（DFT）在B3LYP／6-31G（d）计算水平上对进入I临床试验阶段的T790M EGFR不可逆抑制剂HKI-272及WZ系列抑制剂进行了研究。结果表明，WZ系列抑制剂在参与Michael加成反应的能力、与T790M EGFR形成的氢键的强度等方面，都优于HKI-272。抑制剂中的参与形成氢键的氢键供体N原子所带的NBO电荷与抑制剂的抗肿瘤功效高度相关。

英文摘要：

WZ-series irreversible inhibitors are much more potent against T790M EGFR than HKI-272, one of the inhibitors currently under clinical development. All of them were investigated at the B3LYP/6-31G（d） level by employing G03 so as to reveal the essential factors vital for the potent antitumor activities of the WZ-series inhibitors. It was demonstrated that the WZ-series inhibitors are superior to HKI-272 in the capability to participate in Michael addition reaction. It could be speculated from the calculated results that the strength of H-bond formed between WZ-series inhibitors and T790M EGFR would be stronger than that between HKI-272 and the mutant EGFR. It is worth to note that the values of NBO charge of the H-bond donor in the inhibitors are highly relevant to the antitumor activities of the inhibitors.