title: Novel oxazolo[4,5-g]quinazolin-2(1H)-ones: dual inhibitors of EGFR and Src protein tyrosine kinases.
abstract: Quinazoline-containing derivatives are an important class of synthetic products and represent an attractive scaffold for EGFR inhibitors. A series of oxazolo[4,5-g]quinazolin-2(1H)-one derivatives were synthesized and the EGFR and Src inhibition activities were evaluated using Gefitinib as lead compound. The three most potent compounds 5y, 5l and 5a each inhibited EGFR at the IC(50) value of 61 nM, 67 nM and 78 nM. Among them, 5c also demonstrated excellent inhibition activity against Src with the IC(50) value of 3.1 μM. Several of these derivatives also showed good anti-proliferation effects against KB and A498 cells.
authors: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Xiang, Gulou District, Nanjing 210009, PR China.
authors: Jinsheng
authors: J
authors: Lin
authors: Wei
authors: W
authors: Shen
authors: Jingwei
authors: J
authors: Xue
authors: Juan
authors: J
authors: Sun
authors: Xue
authors: X
authors: Zhang
authors: Can
authors: C
authors: Zhang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D019061:src-Family Kinases