948313-35-7Relevant academic research and scientific papers
Discovery of novel benzimidazoles as potent inhibitors of TIE-2 and VEGFR-2 tyrosine kinase receptors
Hasegawa, Masaichi,Nishigaki, Naohiko,Washio, Yoshiaki,Kano, Kazuya,Harris, Philip A.,Sato, Hideyuki,Mori, Ichiro,West, Rob I.,Shibahara, Megumi,Toyoda, Hiroko,Wang, Liping,Nolte, Robert T.,Veal, James M.,Cheung, Mui
, p. 4453 - 4470 (2008/02/13)
We herein disclose a novel chemical series of benzimidazole-ureas as inhibitors of VEGFR-2 and TIE-2 kinase receptors, both of which are implicated in angiogenesis. Structure-activity relationship (SAR) studies elucidated a critical role for the N1 nitrogen of both the benzimidazole (segment E) and urea (segment B) moieties. The SAR results were also supported by the X-ray crystallographic elucidation of the role of the N1 nitrogen and the urea moiety when the benzimidazole-urea compounds were bound to the VEGFR-2 enzyme. The left side phenyl ring (segment A) occupies the backpocket where a 3-hydrophobic substituent was favored for TIE-2 activity.
