952490-57-2Relevant academic research and scientific papers
Design, synthesis, and evaluation of orally active benzimidazoles and benzoxazoles as vascular endothelial growth factor-2 receptor tyrosine kinase inhibitors
Potashman, Michele H.,Bready, James,Coxon, Angela,Demelfi Jr., Thomas M.,DiPietro, Lucian,Doerr, Nicholas,Elbaum, Daniel,Estrada, Juan,Gallant, Paul,Germain, Julie,Gu, Yan,Harmange, Jean-Christophe,Kaufman, Stephen A.,Kendall, Rick,Kim, Joseph L.,Kumar, Gondi N.,Long, Alexander M.,Neervannan, Seshadri,Patel, Vinod F.,Polverino, Anthony,Rose, Paul,Van Der Plas, Simon,Whittington, Douglas,Zanon, Roger,Zhao, Huilin
, p. 4351 - 4373 (2008/02/13)
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. In this report we describe the synthesis and structure-activity relationship of a series of 2-aminobenzimidazoles and benzoxazoles, culminating in the identification of benzoxazole 22 as a potent and selective VEGFR-2 inhibitor displaying a good pharmacokinetic profile. Compound 22 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).
FUSED AZOLES SUCH AS 2,5-DISUBSTITUTED BENZIMIDAZOLES, BENZOXAZOLES AND BENZOTHIAZOLES AS KINASE INHIBITORS
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Page 157, (2008/06/13)
The invention relates to compounds of the formulae (I) to (III) wherein the substituents are as defined in the specification. These compounds have kinase inhibitory activity, such as VEGFR/KDR inhibitory activity. Accordingly, the compounds of the formulae (I) to (III) would be useful in the prevention and treatment of angiogenesis related disorders, ophthalmological conditions, proliferative diseases, inflammatory diseases, and other pathological conditions as described in the specification.
