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Abstract(s)
Vascular endothelial growth factor receptor 2 (VEGFR2) is a class of tyrosine kinase
receptors, expressed primarily in endothelial cells , and is activated by the specific binding
of VEGF to the VEGFR2 extracellular regulatory domain, undergoing
autophosphorylation, triggering signaling pathways leading to endothelial cell proliferation
and subsequent angiogenesis.111 Small molecules may actas inhibitors by competing for the
ATP-binding si te of the VEGFR2 intracellular tyrosine kinase domain, thereby preventing
the intracellular signaling that leads to angiogenesisYl Herein, we report the synthesis of
nove! nine 1-aryl-3-[2-, 3- or 4-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas as VEGFR2
inhibitors. The compounds presented below, with the arylurea in the meta position to the
thioether, showed the lowest IC50 values (0.4-0.9 ]lM) in enzymatic assays. Using
molecular docking (A) and molecular dynamics simulations, a convincing rationalization
was achieved to explain the highest potency of these compounds.
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Citation
Queiroz, Maria João; Peixoto, Daniela; Calhelha, Ricardo C.; Abreu, Rui M.V.; Froufe, Hugo J.C.; Ferreira, Isabel C.F.R.; Costa, Raquel; Soares, Raquel (2012). Synthesis, docking, enzymatic and cellular assays of thieno[3,2-b]pyridine-thioether-1,3-diarylureas as VEGFR2 inhibitors. In 3º Encontro Nacional de Química Terapêutica e 1st Portuguese-Spanish-Brazilian Meeting on Medicinal Chemistry. Aveiro