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Synthesis and Biological Evaluation of Novel Oxazolo[5,4‐ d ]pyrimidines as Potent VEGFR‐2 Inhibitors
Author(s) -
Deng YaHui,
Xu Dan,
Su YeXiang,
Cheng YiJuan,
Yang YanLi,
Wang XiuYun,
Zhang Juan,
You QiDong,
Sun LiPing
Publication year - 2015
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201400270
Subject(s) - umbilical vein , chemistry , kinase , in vitro , docking (animal) , vegf receptors , angiogenesis , kinase insert domain receptor , inhibitory postsynaptic potential , vascular endothelial growth factor , biochemistry , pharmacology , cancer research , vascular endothelial growth factor a , biology , medicine , nursing , neuroscience
Tumor angiogenesis is mediated by vascular endothelial growth factor receptor (VEGFR) and other protein kinases. Inhibition of these kinases presents an attractive approach for developing anticancer therapeutics. In this work, a series of 2,5,7‐trisubstituted oxazolo[5,4‐ d ]pyrimidines were synthesized, and their inhibitory activities were investigated against VEGFR‐2 and human umbilical vein endothelial cells (HUVEC) in vitro. Compound 9n exhibited the most potent inhibitory activity with IC 50 values of 0.33 and 0.29 μ M for VEGFR‐2 kinase and HUVEC, respectively. A further kinase selectivity assay revealed that these compounds exhibit good VEGFR and moderate EGFR inhibitory activities. Docking analysis suggested a common mode of interaction at the ATP‐binding site of VEGFR‐2.