4-Aryl-5-cyano-2-aminopyrimidines as VEGF-R2 inhibitors: synthesis and biological evaluation

Terry V Hughes; Stuart L Emanuel; Amanda K Beck; Steven K Wetter; Peter J Connolly; Prabha Karnachi; Michael Reuman; Jabed Seraj; Angel R Fuentes-Pesquera; Robert H Gruninger; Steven A Middleton; Ronghui Lin; Jeremy M Davis; David F C Moffat

doi:10.1016/j.bmcl.2007.04.021

4-Aryl-5-cyano-2-aminopyrimidines as VEGF-R2 inhibitors: synthesis and biological evaluation

Bioorg Med Chem Lett. 2007 Jun 15;17(12):3266-70. doi: 10.1016/j.bmcl.2007.04.021. Epub 2007 Apr 10.

Authors

Terry V Hughes¹, Stuart L Emanuel, Amanda K Beck, Steven K Wetter, Peter J Connolly, Prabha Karnachi, Michael Reuman, Jabed Seraj, Angel R Fuentes-Pesquera, Robert H Gruninger, Steven A Middleton, Ronghui Lin, Jeremy M Davis, David F C Moffat

Affiliation

¹ Johnson & Johnson Pharmaceutical Research and Development, L.L.C, PO Box 300, 1000 Route 202, Raritan, NJ 08869, USA. [email protected]

PMID: 17481894
DOI: 10.1016/j.bmcl.2007.04.021

Abstract

A novel series of 4-aryl-5-cyano-2-aminopyrimidines were synthesized and found to have potent VEGF-R2 kinase inhibitory activity. Structure-activity relationships were investigated and compound 14a was shown to be efficacious in a mouse model of corneal neovascularization.

Publication types

Evaluation Study

MeSH terms

Animals
Corneal Neovascularization / drug therapy*
Corneal Neovascularization / pathology
Disease Models, Animal
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology
Enzyme Inhibitors / therapeutic use*
Mice
Pyrimidines / chemical synthesis
Pyrimidines / pharmacology*
Structure-Activity Relationship
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*

Substances

Enzyme Inhibitors
Pyrimidines
Vascular Endothelial Growth Factor Receptor-2