284031-02-3Relevant academic research and scientific papers
New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis
Bold, Guido,Altmann, Karl-Heinz,Frei, J?rg,Lang, Marc,Manley, Paul W.,Traxler, Peter,Wietfeld, Bernhard,Brüggen, Josef,Buchdunger, Elisabeth,Cozens, Robert,Ferrari, Stefano,Furet, Pascal,Hofmann, Francesco,Martiny-Baron, Georg,Mestan, Jürgen,R?sel, Johannes,Sills, Matthew,Stover, David,Acemoglu, Figan,Boss, Eugen,Emmenegger, René,L?sser, Laurent,Masso, Elvira,Roth, Rosemarie,Schlachter, Christian,Vetterli, Werner,Wyss, Dominique,Wood, Jeanette M.
, p. 2310 - 2323 (2000)
The sprouting of new blood vessels, or angiogenesis, is necessary for any solid tumor to grow large enough to cause life-threatening disease. Vascular endothelial growth factor (VEGF) is one of the key promoters of tumor induced angiogenesis. VEGF receptors, the tyrosine kinases Flt-1 and KDR, are expressed on vascular endothelial cells and initiate angiogenesis upon activation by VEGF. 1-Anilino-(4-pyridylmethyl)-phthalazines, such as CGP 79787D (or PTK787/ZK222584), reversibly inhibit Flt-1 and KDR with IC50 values 50 = 34 nM). Modification of the 1-anilino moiety afforded derivatives with higher selectivity for the VEGF receptor tyrosine kinases Flt-1 and KDR compared to the related receptor tyrosine kinases PDGF-R and c-Kit. Since these 1-anilino-(4-pyridylmethyl)phthalazines are orally well absorbed, these compounds qualify for further profiling and as candidates for clinical evaluation.
