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In this study, novel 1-aryl-3-[4-(thieno[3,2-<jats:italic>d<\/jats:italic>]pyrimidin-4-yloxy)phenyl]ureas were synthesized and evaluated for the VEGFR-2 tyrosine kinase inhibition. Three of these compounds showed good VEGFR-2 inhibition presenting low IC<jats:sub>50<\/jats:sub>values (150\u2013199\u2009nM) in enzymatic assays, showing also a significant proliferation inhibition of VEGF-stimulated human umbilical vein endothelial cells (HUVECs) at low concentrations (0.5\u20131\u2009\u00b5M), using the Bromodeoxyuridine (BrdU) assay, not affecting cell viability. The determination of the total and phosphorylated (active) VEGFR-2 was performed by western blot, and it was possible to conclude that the compounds significantly inhibit the phosphorylation of the receptor at 1\u2009\u00b5M pointing to their antiproliferative mechanism of action in HUVECs. The molecular rationale for inhibiting the tyrosine kinase domain of VEGFR-2 was also performed and discussed using molecular docking studies.<\/jats:p>","DOI":"10.1155\/2013\/154856","type":"journal-article","created":{"date-parts":[[2013,7,7]],"date-time":"2013-07-07T21:01:10Z","timestamp":1373230870000},"page":"1-9","source":"Crossref","is-referenced-by-count":4,"title":["1-Aryl-3-[4-(thieno[3,2-<i>d<\/i>]pyrimidin-4-yloxy)phenyl]ureas as VEGFR-2 Tyrosine Kinase Inhibitors: Synthesis, Biological Evaluation, and Molecular Modelling Studies"],"prefix":"10.1155","volume":"2013","author":[{"given":"Pedro","family":"Soares","sequence":"first","affiliation":[{"name":"Centro de Qu\u00edmica, Escola de Ci\u00eancias, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"CIQ\/Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal"}]},{"given":"Raquel","family":"Costa","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica (U38-FCT), Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"}]},{"given":"Hugo J. 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