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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. © 2005 Elsevier Ltd. All rights reserved.
Bioorganic & Medicinal Chemistry Letters 05/2005; 15(9):2203-2207. DOI:10.1016/j.bmcl.2005.03.034 · 2.42 Impact Factor