Anti-VEGF therapy is a clinically validated treatment for age-related macular degeneration (AMD). We have recently reported the discovery of oral VEGFR-2 inhibitors that are selectively distributed to the ocular tissues. Herein we report a further development of those compounds and in particular the validation of the hypothesis that aminoheterocycles such as aminoisoxazoles and aminopyrazoles could also function as effective "hinge" binding moieties leading to a new class of KDR (kinase insert domain containing receptor) inhibitors.
Keywords: KDR; VEGF; Vascular endothelial growth factor receptor 2; amino heterocycles; hinge binding; scaffold morphing.