Abstract
A novel 4-aminopyrimidine-5-carboxaldehyde oxime scaffold with inhibitory activity against VEGFR-2 kinase has been identified. With a 4-fluoro-2-methylindol-5-yloxy group at the 6-position and alkyl groups as the oxime side chains, many analogues showed good potency for VEGFR-2. This series also exhibited antiproliferative activity against cancer cells, causing cell accumulation at the G2/M phase of the cell cycle and preventing cells from entering mitosis. Described here are the chemistry, structure-activity relationships (SAR), and biological testing for this series.
MeSH terms
-
Cell Proliferation / drug effects
-
HeLa Cells
-
Humans
-
Molecular Structure
-
Oximes / chemical synthesis
-
Oximes / chemistry*
-
Oximes / pharmacology*
-
Protein Kinase Inhibitors / chemical synthesis*
-
Protein Kinase Inhibitors / chemistry
-
Protein Kinase Inhibitors / pharmacology*
-
Pyrimidines / chemical synthesis*
-
Pyrimidines / pharmacology*
-
Structure-Activity Relationship
-
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
-
Vascular Endothelial Growth Factor Receptor-2 / metabolism
Substances
-
Oximes
-
Protein Kinase Inhibitors
-
Pyrimidines
-
Vascular Endothelial Growth Factor Receptor-2