Evolution of a New Class of VEGFR-2 Inhibitors from Scaffold Morphing and Redesign.
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.
Global Discovery Chemistry, Novartis Institutes for Biomedical Research , 100 Technology Square, Cambridge, Massachusetts 02139, United States.
Nello
N
Mainolfi
Global Discovery Chemistry, Novartis Institutes for Biomedical Research , 100 Technology Square, Cambridge, Massachusetts 02139, United States.
Rajeshri
R
Karki
Ophthalmology, Novartis Institutes for Biomedical Research , 500 Technology Square, Cambridge, Massachusetts 02139, United States.
Fang
F
Liu
Ophthalmology, Novartis Institutes for Biomedical Research , 500 Technology Square, Cambridge, Massachusetts 02139, United States.
Karen
K
Anderson
KDR; VEGF; Vascular endothelial growth factor receptor 2; amino heterocycles; hinge binding; scaffold morphing