VEGF receptor tyrosine kinase inhibitors

Schlaeppi JM, Wood JM. Targeting vascular endothelial growth factor (VEGF) for anti-tumor therapy, by anti-VEGF neutralizing monoclonal antibodies or by VEGF receptor tyrosine kinase inhibitors. Cancer Metastasis Rev 1999 18 4734-81. 

Substituted quinazolin-4(3H)-ones, (V), effective as CXCR3 chemokine receptor modulators and anthranilic acid amides, (VI), effective as VEGF-receptor tyrosine kinase inhibitors were prepared by Medina (5) and Bold (6), respectively, and used in the treatment of diabetic retinopathy and age-related macular degeneration. 

Additional 2-amino-nicotinamide derivatives, (I) and (II), prepared by Askew (1) and Manley (2), respectively, were effective as VEGF receptor tyrosine kinase inhibitors and used to treat diseases associated with deregulated angiogenesis. 

Batchelor T, Sorensen A et al. (2008) A multidisciplinary phase II study of AZD2171 (cediranib), an oral Pan-VEGF receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. Proc Am Assoc Cancer Res (AACR) 2008 Annual Meeting. Abstract LB-247... 

Batchelor TT, Sorensen AG etal. (2007) AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11(1) 83-95... 

Drevs J, Konerding MA et al. (2004) The VEGF receptor tyrosine kinase inhibitor, ZD6474, inhibits angiogenesis and affects microvascular architecture within an orthotopi-cally implanted renal cell carcinoma. Angiogenesis 7(4) ... 

Similar chemistry was used to synthesize pyridyl(methyl)phthalazines, 193, inhibitors of the VEGF receptor tyrosine kinase. The active inhibitors 193 were formed by condensation of 192 with hydrazine, followed by POCI3 chlorination. <00JMC2310>. Furthermore, a simple substitution reaction with p-chloroaniline gave anilinophthalazine 194. 

Wood JM, Bold G, Buchdunger E, et al. PTK787/ZK 222584, a novel and potent inhibitor of VEGF receptor tyrosine kinases, impairs VEGF-induced responses and tumor growth after oral administration. Cancer Res 2000 60 2178-2189. 

The indolin-2-one template, a feature of inhibitors of the receptor tyrosine kinases of Her-2, VEGF, and EGF, was used by GlaxoSmithKline scientists as a starting point to design a series of analogs from which the selective CDK-2 inhibitor 60 (IC50 = 0.06 xM) was identified. A thorough analysis of... 

Although these neurotrophic factors stimulate neurogenesis after brain ischemia, chronic intraventricular administration of peptides or proteins is inappropriate for human therapies because of insufficient penetration into brain tissue. Since various receptor tyrosine kinases, including EGF, FGF-2, BDNF, and VEGF receptors, are negatively regulated by protein tyrosine phosphatases (Ostman and Bohmer, 2001), inhibitors for protein tyrosine phosphatases possibly promote... 

Cediranib [19] (http //www.astrazeneca.com/media/ itemId=6746833) is an orally bioavailable tyrosine kinase inhibitor of all three VEGF receptors (VEGFRl-3),... 

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