osimertinib and indole

EGFR inhibitors represent a significant milestone for treatment of non-small cell lung cancer, however, they suffer from the acquired drug resistance. Utilizing osimertinib as the lead compound, this work has explored the structural modifications on the indole and pyrimidine rings of osimertinib to generate novel osimertinib derivatives. The in vitro enzymatic and cellular studies showed that the derivatives possessed high selectivity towards double mutant EGFR and potent antitumor activity. Particularly, compound 6b-1, the most active compound, exhibited excellent inhibitory activity against double mutant EGFR (IC

Topics: Acrylamides; Aniline Compounds; Antineoplastic Agents; Cell Proliferation; Dose-Response Relationship, Drug; Drug Discovery; Drug Screening Assays, Antitumor; ErbB Receptors; Humans; Indoles; Molecular Docking Simulation; Molecular Structure; Mutation; Protein Kinase Inhibitors; Pyrimidines; Structure-Activity Relationship; Tumor Cells, Cultured