Angiogenesis is closely related to the proliferation or metastasis of cancer, and also the pathogenesis and the progression of rheumatoid arthritis and age-related macular degeneration. The pathway of signal transduction through vascular endothelial growth factor (VEGF) plays a very important role in pathological angiogenesis. We previously reported that 4-pyridylmethylthio derivatives 1 were potent VEGFR2 inhibitors and they had a similar conformation to PTK787 (2) by their intramolecular nonbonded S-O interaction. Although these derivatives showed activities in vitro and efficacies in various animal disease models in vivo, they also inhibited CYP which caused drug-drug interaction. To improve the CYP inhibition, we investigated the syntheses and biological evaluations of various derivatives. In this meeting, we will report the detailed optimization of the derivatives and the result of animal disease models.

Novel VEGFR2 inhibitors: Pyridylmethylthio derivatives with intramolecular nonbonded S-O interaction

240th National Meeting (2010)

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