Design, synthesis and biological evaluation of biphenyl urea derivatives as novel VEGFR-2 inhibitors
Design, synthesis and biological evaluation of biphenyl urea derivatives as novel VEGFR-2 inhibitors
复制标题
新型 VEGFR-2 抑制剂联苯脲衍生物的设计、合成和生物学评价
DOI：
10.1039/c3md00192j
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Zhang Jie
中科院分区：
文献类型：
--
作者：
Wang Cheng;Dong Jinyun;Zhang Yanmin;Wang Fang;Gao Hongping;Li Pengfei;Wang Sicen;Zhang Jie
VEGFR-2在血管生成中起着至关重要的作用，VEGFR-2抑制剂已被广泛用于癌症的治疗。在我们继续努力寻找有效的新型VEGFR-2抑制剂作为抗肿瘤药物的过程中，我们已经确定了一种具有联苯支架的有效先导化合物（HMQ-16）。HMQ-16中的芳基氨基甲酰被尿素片段重排和取代，产生了一系列新的VEGFR-2抑制剂。为了增强与VEGFR-2的亲和力，将4 ' -乙酰基转化为肟基。设计并合成了14种联苯脲衍生物作为VEGFR-2抑制剂。其中6个（T2、T5、T7、T9、T11、T14）表现出与索拉非尼相当的VEGFR-2抑制活性。化合物T7作用最强，IC50值为1.08 nM。酶和细胞实验表明T7有潜力作为有价值的先导化合物进行进一步优化。
VEGFR-2 plays a critical role in vasculogenesis and VEGFR-2 inhibitors have been widely used in the treatment of cancer. In our continued efforts to search for potent and novel VEGFR-2 inhibitors as antitumor agents, we have identified a potent lead compound (HMQ-16) bearing a biphenyl scaffold. Rearrangement and replacement of arylcarbamoyl in HMQ-16 with a urea moiety generated a series of novel VEGFR-2 inhibitors. In order to enhance the affinity with VEGFR-2, the 4′-acetyl group was converted to an oxime group. Fourteen biphenyl urea derivatives were designed and synthesized as potent VEGFR-2 inhibitors. Six of them (T2, T5, T7, T9, T11, T14) exhibited potent VEGFR-2 inhibitory activity comparable to that of sorafenib. Compound T7 was the most potent with an IC50 value of 1.08 nM. The enzymatic and cellular assays suggested that T7 has potential as a valuable lead compound for further optimization.
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DOI：
10.1007/978-3-540-37696-5_19
发表时间：
2007
期刊：
Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer
影响因子：
--
作者：
D. Noonan;R. Benelli;A. Albini
通讯作者：
D. Noonan;R. Benelli;A. Albini
影响因子：
2.7
作者：
Jie Zhang;Yanmin Zhang;San-qi Zhang;Sicen Wang;Langchong He
通讯作者：
Jie Zhang;Yanmin Zhang;San-qi Zhang;Sicen Wang;Langchong He
DOI：
10.2174/138955711797068355
发表时间：
2011-09
期刊：
Mini reviews in medicinal chemistry
影响因子：
--
作者：
J. Zhang;Y. Shan;X. Pan;L. He
通讯作者：
J. Zhang;Y. Shan;X. Pan;L. He
DOI：
10.2174/157340611796150914
发表时间：
2011-06
期刊：
Medicinal chemistry (Shariqah (United Arab Emirates))
影响因子：
--
作者：
Jie Zhang;Yanmin Zhang;Xiaoyan Pan;Sicen Wang;Langchong He
通讯作者：
Jie Zhang;Yanmin Zhang;Xiaoyan Pan;Sicen Wang;Langchong He
影响因子：
2.7
作者：
Tripathy, Rabindranath;Ghose, Arup;Mallamo, John P.
通讯作者：
Mallamo, John P.