Synthesis and Biological Evaluation of Novel Oxazolo[5,4-d]pyrimidines as Potent VEGFR-2 Inhibitors
Synthesis and Biological Evaluation of Novel Oxazolo[5,4-d]pyrimidines as Potent VEGFR-2 Inhibitors
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作为有效 VEGFR-2 抑制剂的新型恶唑并[5,4-d]嘧啶的合成和生物学评价
DOI：
10.1002/cbdv.201400270
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发表时间：
2015-04-01
影响因子：
2.9
通讯作者：
Sun, Li-Ping
中科院分区：
文献类型：
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作者：
Deng, Ya-Hui;Xu, Dan;Sun, Li-Ping
肿瘤血管生成是由血管内皮生长因子受体（VEGFR）和其他蛋白激酶介导的。这些激酶的抑制为开发抗癌疗法提供了有吸引力的方法。本工作合成了一系列2，5，7-三取代恶唑并[5，4-d]嘧啶类化合物，并研究了它们对VEGFR-2和人脐静脉内皮细胞（HUVEC）的体外抑制活性。化合物9 n对VEGFR-2激酶和HUVEC的IC_（50）分别为0.33和0.29M。进一步的激酶选择性测定显示，这些化合物表现出良好的VEGFR和中度EGFR抑制活性。对接分析表明，在VEGFR-2的ATP结合位点的相互作用的共同模式。
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 IC50 values of 0.33 and 0.29M for VEGFR-2kinase 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.