Design and synthesis of 3,7-diarylimidazopyridines as inhibitors of the VEGF-receptor KDR
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Acknowledgments
We thank Kenneth D. Anderson for solubility determination. We also thank Dr. Art Coddington, Dr. Chuck Ross and Dr. Harri Ramjit for mass spectral analyses.
References (17)
- et al.
Biochem. Biophys. Res. Commun.
(1993) Dermatol. Sci.
(2000)- et al.
Int. J. Cancer
(2002) - et al.
J. Biol. Chem.
(1999) - et al.
J. Path.
(2001) - et al.
Nature
(2000)Nature Med.
(1995)
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