Abstract
A library of pyrido[2,3-d]pyrimidines was designed as inhibitors of FGFR3 tyrosine kinase allowing possible interactions with an unexploited region of the ATP binding-site. This library was built-up with an efficient step of click-chemistry giving easy access to triazole-based compounds bearing a large panel of substituents. Among the 27 analogues synthesized, more than half exhibited 55-89% inhibition of in vitro FGFR3 kinase activity at 2 microM and one (19g) was able to inhibit auto-phosphorylation of mutant FGFR3-K650M in transfected HEK cells.
MeSH terms
-
Binding Sites
-
Cell Line
-
Drug Design*
-
Humans
-
Molecular Structure
-
Protein Kinase Inhibitors / chemical synthesis
-
Protein Kinase Inhibitors / chemistry
-
Protein Kinase Inhibitors / pharmacology*
-
Protein-Tyrosine Kinases / antagonists & inhibitors*
-
Pyridines / chemical synthesis
-
Pyridines / chemistry*
-
Pyridines / pharmacology*
-
Pyrimidines / chemical synthesis
-
Pyrimidines / chemistry*
-
Pyrimidines / pharmacology*
-
Recombinant Proteins / antagonists & inhibitors
-
Small Molecule Libraries
-
Stereoisomerism
-
Structure-Activity Relationship
-
Triazoles / chemistry*
Substances
-
1-tert-butyl-3-(6-(3,5-dimethoxyphenyl)-2-((1-((1-methylpiperidin-3-yl)methyl)-1H-1,2,3-triazol-4-yl)methylamino)pyrido(2,3-d)pyrimidin-7-yl)urea
-
Protein Kinase Inhibitors
-
Pyridines
-
Pyrimidines
-
Recombinant Proteins
-
Small Molecule Libraries
-
Triazoles
-
Protein-Tyrosine Kinases