Novel 4-amino-furo[2,3-d]pyrimidines as Tie-2 and VEGFR2 dual inhibitors

  • Bioorg Med Chem Lett. 2005 May 2;15(9):2203-7. doi: 10.1016/j.bmcl.2005.03.034.
Yasushi Miyazaki  1 ,  Shinichiro Matsunaga ,  Jun Tang ,  Yutaka Maeda ,  Masato Nakano ,  Rocher J Philippe ,  Megumi Shibahara ,  Wei Liu ,  Hideyuki Sato ,  Liping Wang ,  Robert T Nolte
Affiliations
  • 1. GlaxoSmithKline K.K., Tsukuba Research Laboratories, 43, Wadai, Tsukuba 300-4247, Ibaraki, Japan. [email protected]
PMID: 15837294 DOI: 10.1016/j.bmcl.2005.03.034
Abstract

A novel class of furo[2,3-d]pyrimidines has been discovered as potent dual inhibitors of TIE-2 and VEGFR2 Receptor Tyrosine Kinases (TK) and a diarylurea moiety at 5-position shows remarkably enhanced activity against both Enzymes. One of the most active compounds, 4-amino-3-(4-((2-fluoro-5-(trifluoromethyl)phenyl)amino-carbonylamino)phenyl)-2-(4-methoxyphenyl)furo[2,3-d]pyrimidine (7k) is <3 nM on both TK receptors and the activity is rationalized based on the X-ray crystal structure.