Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 7, Issue 4, Pages 363-367Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.5b00486
Keywords
Vascular endothelial growth factor receptor 2; VEGF; KDR; hinge binding; scaffold morphing; amino heterocycles
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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.
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