Synthesis and biological evaluation of a triazole-based library of pyrido[2,3-d]pyrimidines as FGFR3 tyrosine kinase inhibitors?

Organic & Biomolecular Chemistry Pub Date: 2010-03-11 DOI: 10.1039/B923882D

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 μM and one (19g) was able to inhibit auto-phosphorylation of mutant FGFR3-K650M in transfected HEK cells.

Graphical abstract: Synthesis and biological evaluation of a triazole-based library of pyrido[2,3-d]pyrimidines as FGFR3 tyrosine kinase inhibitors
Recommended Literature