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ID: ALA3992524

Journal: Eur J Med Chem

Title: Discovery of novel anti-angiogenesis agents. Part 6: Multi-targeted RTK inhibitors.

Authors: Zhang L, Shan Y, Li C, Sun Y, Su P, Wang J, Li L, Pan X, Zhang J.

Abstract: Angiogenesis is modulated by a multitude of pro-angiogenic factors including VEGFR-2, Tie-2, and EphB4. Moreover, their crosstalk also had been well elaborated. We have identified several diarylurea-based VEGFR-2 inhibitors as potential anti-angiogenesis agents. As a continuation to our previous research, two series of diaryl malonamide and diaryl thiourea derivatives have been developed as multiplex VEGFR-2/Tie-2/EphB4 inhibitors. Interestingly, the biological evaluation indicated that several compounds bearing trifluoromethyl or trifluoromethoxyl exhibited promising multiplex inhibition against angiogenesis-related VEGFR-2, Tie-2, and EphB4. The representative compound (18a) displayed both potent multi-targeted RTK inhibition and considerable antiproliferative activities against human umbilical vein endothelial cells (EA.hy926). These results will contribute to the discovery of novel muti-targeted anti-angiogenesis agents.

CiteXplore: 28068599

DOI: 10.1016/j.ejmech.2016.12.059