A series of A-ring-modified lamellarin N analogues were designed, synthesized, and evaluated as potential noncovalent inhibitors of the EGFR T790M/L858R mutant, a causal factor in the drug-resistant non-small cell lung cancer. Several water-soluble ammonium- or guanidinium-tethered analogues exhibited good kinase inhibitory activities. The most promising analogue, 14f, displayed an excellent inhibitory profile against the T790M/L858R mutant [IC₅₀ (WT) = 31.8 nM; IC₅₀ (T790M/L858R) = 8.9 nM]. The effects of A-ring-substituents on activity were rationalized by docking studies.

中文翻译：

---

设计，合成和评估A环修饰的lamellarin N类似物作为EGFR T790M / L858R突变体的非共价抑制剂

设计，合成和评估了一系列A环修饰的lamellarin N类似物，作为EGFR T790M / L858R突变体的潜在非共价抑制剂，EGFR T790M / L858R突变体是耐药性非小细胞肺癌的致病因素。几种水溶性铵盐或胍盐系的类似物表现出良好的激酶抑制活性。最有前途的类似物14f对T790M / L858R突变体表现出优异的抑制作用[IC ₅₀（WT）= 31.8 nM; IC ₅₀（T790M / L858R）= 8.9 nM]。通过对接研究合理化了A环取代基对活性的影响。