Mannion Michael, Raeppel Stéphane, Claridge Stephen, Zhou Nancy, Saavedra Oscar, Isakovic Ljubomir, Zhan Lijie, Gaudette Frédéric, Raeppel Franck, Déziel Robert, Beaulieu Normand, Nguyen Hannah, Chute Ian, Beaulieu Carole, Dupont Isabelle, Robert Marie-France, Lefebvre Sylvain, Dubay Marja, Rahil Jubrail, Wang James, Ste-Croix Hélène, Robert Macleod A, Besterman Jeffrey M, Vaisburg Arkadii
Department of Medicinal Chemistry, MethylGene Inc, Montréal, QC, Canada.
Bioorg Med Chem Lett. 2009 Dec 1;19(23):6552-6. doi: 10.1016/j.bmcl.2009.10.040. Epub 2009 Oct 13.
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.
设计并合成了一系列靶向c-Met和VEGFR2酪氨酸激酶的N-(4-(6,7-二取代喹啉-4-基氧基)-3-氟苯基)-2-氧代-3-苯基咪唑烷-1-甲酰胺。这些化合物对这两种酶具有强效作用，体外IC(50)值在低纳摩尔范围内，具有良好的药代动力学特征，并且在小鼠的几种人肿瘤异种移植模型中显示出高体内疗效。
