N-(4-(6,7-Disubstituted-quinolin-4-yloxy)-3-fluorophenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: a novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitors.

Abstract

A series of N-(4-(6,7-disubstituted-quinolin-4-yloxy)-3-fluorophenyl)-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.2009.10.040

Cite this paper

@article{Mannion2009N467Disubstitutedquinolin4yloxy3fl, title={N-(4-(6,7-Disubstituted-quinolin-4-yloxy)-3-fluorophenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: a novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitors.}, author={Michael Mannion and St{\'e}phane L. Raeppel and Stephen Claridge and Nancy Z Zhou and Oscar M Saavedra and Ljubomir Isakovic and Lijie Zhan and Fr{\'e}d{\'e}ric Gaudette and Franck Raeppel and Robert D{\'e}ziel and Normand Beaulieu and Hannah Nguyen and Ian C. Chute and Carole Beaulieu and Isabelle Dupont and M -F. 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 23}, pages={6552-6} }