1YWN

Vegfr2 in complex with a novel 4-amino-furo[2,3-d]pyrimidine

Summary for 1YWN

• Entry DOI: 10.2210/pdb1ywn/pdb
• Related: 1vr2 1y6a 1y6b
• Descriptor: Vascular endothelial growth factor receptor 2, N-{4-[4-AMINO-6-(4-METHOXYPHENYL)FURO[2,3-D]PYRIMIDIN-5-YL]PHENYL}-N'-[2-FLUORO-5-(TRIFLUOROMETHYL)PHENYL]UREA (3 entities in total)
• Functional Keywords: transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cell junction . Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted . Isoform 3: Secreted: P35968
• Total number of polymer chains: 1
• Total formula weight: 36892.18

Authors

Miyazaki, Y.,Matsunaga, S.,Tang, J.,Maeda, Y.,Nakano, M.,Philippe, R.J.,Shibahara, M.,Liu, W.,Sato, H.,Wang, L.,Nolte, R.T. (deposition date: 2005-02-18, release date: 2005-08-23, Last modification date: 2024-10-16)

Primary citation

Miyazaki, Y.,Matsunaga, S.,Tang, J.,Maeda, Y.,Nakano, M.,Philippe, R.J.,Shibahara, M.,Liu, W.,Sato, H.,Wang, L.,Nolte, R.T.
Novel 4-amino-furo[2,3-d]pyrimidines as Tie-2 and VEGFR2 dual inhibitors
Bioorg.Med.Chem.Lett., 15:2203-2207, 2005

PubMed 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.

PubMed: 15837294
DOI: 10.1016/j.bmcl.2005.03.034

Experimental method

X-RAY DIFFRACTION (1.71 Å)