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861875-60-7

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A Novel Potent Oral Series of VEGFR2 Inhibitors Abrogate Tumor Growth by Inhibiting Angiogenesis
This paper describes the identification of 6-(pyrimidin-4-yloxy)-naphthalene-1-carboxamides as a new class of potent and selective human vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitors. In biochemical and cellular assays, the compounds exhibit single-digit nanomolar potency toward VEGFR2. Compounds of this series show good exposure in rodents when dosed orally. They potently inhibit VEGF-driven angiogenesis in a chamber model and rodent tumor models at daily doses of less than 3 mg/kg by targeting the tumor vasculature as demonstrated by ELISA for TIE-2 in lysates or by immunohistochemical analysis. This novel series of compounds shows a potential for the treatment of solid tumors and other diseases where angiogenesis plays an important role.
Bold, Guido,Schnell, Christian,Furet, Pascal,McSheehy, Paul,Brüggen, Josef,Mestan, Jürgen,Manley, Paul W.,Drückes, Peter,Burglin, Marion,Dürler, Ursula,Loretan, Jacqueline,Reuter, Robert,Wartmann, Markus,Theuer, Andreas,Bauer-Probst, Beatrice,Martiny-Baron, Georg,Allegrini, Peter,Goepfert, Arnaud,Wood, Jeanette,Littlewood-Evans, Amanda
p. 132 - 146
(2016/01/28)

COMBINATIONS COMPRISING A VEGF RECEPTOR INHIBITOR
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Page/Page column 21

(2008/06/13)

BICYCLIC AMIDES AS KINASE INHIBITORS
The invention relates to compounds of formula (I) and their use in the treatment of the animal or human body, to pharmaceutical compositions comprising a compound of formula I and to the use of a compound of formula I for the preparation of pharmaceutical compositions for use in the treatment of protein kinase dependent diseases, especially of proliferative diseases, such as in particular tumour diseases.
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Page/Page column 42

(2010/11/08)

COMPOUNDS AND METHODS OF USE
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Page/Page column 205

(2008/06/13)

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Solubility:≥42.4 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH

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