Synthesis and Biological Evaluation of Novel Oxazolo[5,4‐d]pyrimidines as Potent VEGFR‐2 Inhibitors |
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| Authors: | Ya‐Hui Deng Dan Xu Ye‐Xiang Su Yi‐Juan Cheng Yan‐Li Yang Xiu‐Yun Wang Juan Zhang Qi‐Dong You Li‐Ping Sun |
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| Institution: | 1. Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P.?R. China;2. Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, P.?R. China (phone: +86‐25‐83271445;3. fax: +86‐25‐83271351);4. School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, P.?R. China |
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| Abstract: | 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 oxazolo5,4‐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 IC50 values of 0.33 and 0.29 μM 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. |
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| Keywords: | Oxazolo[5 4‐d]pyrimidines VEGFR‐2 Inhibitor Antiproliferative activity Antitumor activity |
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