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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.

Authors :
Raeppel S
Claridge S
Saavedra O
Gaudette F
Zhan L
Mannion M
Zhou N
Raeppel F
Granger MC
Isakovic L
Déziel R
Nguyen H
Beaulieu N
Beaulieu C
Dupont I
Robert MF
Lefebvre S
Dubay M
Rahil J
Wang J
Ste-Croix H
Robert Macleod A
Besterman J
Vaisburg A
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2009 Mar 01; Vol. 19 (5), pp. 1323-8. Date of Electronic Publication: 2009 Jan 27.
Publication Year :
2009

Abstract

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.

Details

Language :
English
ISSN :
1464-3405
Volume :
19
Issue :
5
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
19211249
Full Text :
https://doi.org/10.1016/j.bmcl.2009.01.068