Heteroarylether 1,3-diarylureas in the thieno[3,2-d]pyrimidine series as VEGFR2 tyrosine Kinase inhibitors: synthesis, docking studies, enzymatic and cellular assays

A number of thienopyrimidines derivatives have shown potent YEGFR2 (Vascular Endothelium Growth Factor Receptor2) inhibition activity [ 1]. YEGF is a surrogate marker of angiogenesis that activates VEGFR2 in endothelial cells. VEGF induces proliferation, migration and anastomosis of these cells. Here we present the synthesis of new l-aryl-3-[4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl]ureas, by reaction of 4-aminophenol with 4-chlorothieno[3,2-d]pyrimidine giving compound 1, which was reacted with arylisocyanates to give the corresponding I ,3-diarylureas 2a-c (Scheme).