Discovery of 6-arylurea-2-arylbenzoxazole and 6-arylurea-2-arylbenzimidazole derivatives as angiogenesis inhibitors: design, synthesis and in vitro biological evaluation.

Discovery of 6-arylurea-2-arylbenzoxazole and 6-arylurea-2-arylbenzimidazole derivatives as angiogenesis inhibitors: design, synthesis and in vitro biological evaluation. ChemMedChem. 2019 May 26;: Authors: Jin Y, Zi M, Liu F, Wu D, Li K, Zhang D, Zhu C, Zhang Z, Li L, Zhang C, Xie M, Lin J, Zhang J Abstract Herein, we embarked on a structural optimization campaign aiming at the discovery of novel anti-angiogenesis agents with previously reported imidazole kinase inhibitors as a lead compound. A library of 29 compounds has been synthesized. Several title compounds exhibited selective inhibitory activities against VEGFR-2 kinase than EGFR kinases, which also displayed selective anti-proliferation potency against three cancer cells. The newly synthesized compounds were evaluated for anti-angiogenesis capability by CAM assay. Among them, compound 5n showed the most potent anti-angiogenesis ability, the efficient cytotoxic activities (in vitro against HUVEC, H1975, A549 and Hela cell lines with IC50 values of 8.46, 1.40, 7.61, and 0.28 µM, respectively), and acceptable VEGFR-2 kinase inhibition (IC50 = 0.25 µM). The molecular docking analysis revealed d 5n is a Type II inhibitor of VEGFR-2 kinase. In general, these results indicated these 6-arylurea-2-arylbenzoxazole/benzimidazole derivatives are promising inhibitors of VEGFR-2 kinase for the potential treatment of anti-angiogenesis. PMID: 31131561 [PubMed - as supplied by publ...
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research