N-(3-fluoro-4-(2-arylthieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: a novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitors.


A series of N-(3-fluoro-4-(2-arylthieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides targeting c-Met and VEGFR2 tyrosine kinases was designed and synthesized. The compounds were potent against these two enzymes with IC(50) values in the low nanomolar range in vitro, possessed favorable pharmacokinetic profiles and showed high efficacy in vivo in several human tumor xenograft models in mice.

DOI: 10.1016/j.bmcl.2009.01.068

Cite this paper

@article{Raeppel2009N3fluoro42arylthieno32bpyridin7ylo, title={N-(3-fluoro-4-(2-arylthieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: a novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitors.}, author={St{\'e}phane L. Raeppel and Stephen Claridge and Oscar M Saavedra and Fr{\'e}d{\'e}ric Gaudette and Lijie Zhan and Michael Mannion and Nancy Z Zhou and Franck Raeppel and Marie-Claude Granger and Ljubomir Isakovic and Robert D{\'e}ziel and Hannah Nguyen and Normand Beaulieu and Carole Beaulieu and Isabelle Dupont and Marie-France Robert and Sylvain Lefebvre and Marja M. Dubay and Jubrail Rahil and James J. L. Wang and H{\'e}l{\`e}ne Ste-Croix and A Robert Macleod and Jeffrey M. Besterman and Arkadii F Vaisburg}, journal={Bioorganic & medicinal chemistry letters}, year={2009}, volume={19 5}, pages={1323-8} }