OTAVAchemicals Catalogue Number: 1156358
CAS Registry Number: 769960-39-6
Purity: 95%+ (HPLC)
Ref.: Potashman et al. Design, Synthesis, and Evaluation of Orally Active Benzimidazoles and Benzoxazoles as Vascular Endothelial Growth Factor-2 Receptor Tyrosine Kinase Inhibitors. Journal of Medicinal Chemistry (2007), 50, 4351-4373
Abstract: Inhibition of the VEGF signaling pathway has become a valuable approach in the treatment of cancers. Guided by X-ray crystallography and molecular modeling, a series of 2- aminobenzimidazoles and 2-aminobenzoxazoles were identified as potent inhibitors of VEGFR-2 (KDR) in both enzymatic and HUVEC cellular proliferation assays. The synthesis and structure-activity relationship of a series of 2-aminobenzimidazoles and benzoxazoles, culminating in the identification of a benzoxazole (structure above) as a potent and selective VEGFR-2 inhibitor displaying a good pharmacokinetic profile, is described. This compound demonstrated efficacy in both the murine matrigel model for vascular permeability (79% inhibition observed at 100 mg/kg) and the rat corneal angiogenesis model (ED50 = 16.3 mg/kg).