69627-03-8Relevant articles and documents
Synthesis, antiangiogenesis evaluation and molecular docking studies of 1-aryl-3-[(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas: Discovery of a new substitution pattern for type II VEGFR-2 Tyr kinase inhibitors
Machado, Vera A.,Peixoto, Daniela,Costa, Raquel,Froufe, Hugo J.C.,Calhelha, Ricardo C.,Abreu, Rui M.V.,Ferreira, Isabel C.F.R.,Soares, Raquel,Queiroz, Maria-Jo?o R.P.
, p. 6497 - 6509 (2015)
The synthesis and biological evaluation of novel 1-aryl-3-[2-, 3- or 4-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 3, 4 and 5 as VEGFR-2 tyrosine kinase inhibitors, are reported. The 1-aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 4a-4h, with the arylurea in the meta position to the thioether, showed the lowest IC50 values in enzymatic assays (10-206 nM), the most potent compounds 4d-4h (IC50 10-28 nM) bearing hydrophobic groups (Me, F, CF3 and Cl) in the terminal phenyl ring. A convincing rationalization was achieved for the highest potent compounds 4 as type II VEGFR-2 inhibitors, based on the simultaneous presence of: (1) the thioether linker and (2) the arylurea moiety in the meta position. For compounds 4, significant inhibition of Human Umbilical Vein Endothelial Cells (HUVECs) proliferation (BrdU assay), migration (wound-healing assay) and tube formation were observed at low concentrations. These compounds have also shown to increase apoptosis using the TUNEL assay. Immunostaining for total and phosphorylated (active) VEGFR-2 was performed by Western blotting. The phosphorylation of the receptor was significantly inhibited at 1.0 and 2.5 μM for the most promising compounds. Altogether, these findings point to an antiangiogenic effect in HUVECs.
NITROGEN-CONTAINING FUSED CYCLIC COMPOUND, PREPARATION METHOD THEREFOR AND USE THEREOF
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, (2022/01/03)
The present invention relates to a nitrogen-containing fused ring compound, a preparation method and use thereof. Specifically, the present invention relates to a compound having the structure of Formula (X), a stereoisomer, tautomer or mixture thereof, a pharmaceutically acceptable salt, co-crystal, polymorph or solvate thereof, or a stable isotope derivative, metabolite or prodrug thereof. The compound of the invention may have the structure of Formula (I) or Formula (II). These compounds are useful for the treatment of an abnormal cell proliferation disease (e.g., cancer). ????????R-L-R3?????(X)
Polysubstituted quinolone compounds, and preparation method and use thereof
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, (2017/09/19)
The invention provides polysubstituted quinolone compounds, and a preparation method and a use thereof, and concretely provides a polysubstituted quinolone compound represented by formula I, and optical isomers, pharmaceutically acceptable salts or solvates thereof. All groups in the formula I are defined in the description. The quinolone compound has excellent c-Met inhibition activity, and can be used for treating c-Met activity or expression level corrected diseases.