712294-58-1Relevant academic research and scientific papers
Discovery of novel VEGFR-2 inhibitors. Part II: Biphenyl urea incorporated with salicylaldoxime
Gao, Hongping,Su, Ping,Shi, Yaling,Shen, Xiuxiu,Zhang, Yanmin,Dong, Jinyun,Zhang, Jie
, p. 232 - 240 (2014/12/12)
A series of novel VEGFR-2 inhibitors containing oxime as hinge binding fragment were described. A strategy of pseudo six-membered ring formed through intramolecular hydrogen bond was employed to mimic the planar quinazoline. The oxime group was firstly introduced to interact with hinge region of VEGFR-2. Most of compounds tested showed moderate to high VEGFR-2 inhibitory activity. In particular, 12l, 12p and 12y exhibited significant enzymatic inhibitory activity as well as potent antiproliferative activity against cancer cells. Molecular docking suggested that the salicylaldoxime formed two hydrogen bonds with hinge region. These biphenylureas could serve as promising lead compounds for developing novel anticancer agents.
Biphenyl derivatives incorporating urea unit as novel VEGFR-2 inhibitors: Design, synthesis and biological evaluation
Wang, Chen,Gao, Hongping,Dong, Jinyun,Zhang, Yanmin,Su, Ping,Shi, Yaling,Zhang, Jie
, p. 277 - 284 (2014/01/17)
A series of novel biphenyl urea derivates were synthesized and investigated for their potential to inhibit vascular endothelial growth factor receptor-2 (VEGFR-2). In particular, A7, B3 and B4 displayed significant enzymatic inhibitory activities, with IC50 values of 4.06, 4.55 and 5.26 nM. Compound A7 exhibited potent antiproliferative activity on several cell lines. SAR study suggested that the introduction of methyl at ortho-position of the biphenyl urea and tertiary amine moiety could improve VEGFR-2 inhibitory activity and antitumor effects. Molecular docking indicated that the urea moiety formed four hydrogen bonds with DFG residue. These biphenyl ureas could serve as promising lead compounds for further optimization.
Design, synthesis and biological evaluation of biphenyl urea derivatives as novel VEGFR-2 inhibitors
Wang, Chen,Dong, Jinyun,Zhang, Yanmin,Wang, Fang,Gao, Hongping,Li, Pengfei,Wang, Sicen,Zhang, Jie
supporting information, p. 1434 - 1438 (2013/11/19)
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 IC 50 value of 1.08 nM. The enzymatic and cellular assays suggested that T7 has potential as a valuable lead compound for further optimization.
