Hetaryl imidazoles: a novel dual inhibitors of VEGF receptors I and II

Alexander S Kiselyov; Marina Semenova; Victor V Semenov; Evgueni Piatnitski; Shawn Ouyang

doi:10.1016/j.bmcl.2005.11.033

Hetaryl imidazoles: a novel dual inhibitors of VEGF receptors I and II

Bioorg Med Chem Lett. 2006 Mar 1;16(5):1440-4. doi: 10.1016/j.bmcl.2005.11.033.

Authors

Alexander S Kiselyov¹, Marina Semenova, Victor V Semenov, Evgueni Piatnitski, Shawn Ouyang

Affiliation

¹ Small Molecule Drug Discovery, Chemical Diversity, Inc., 11558 Sorrento Valley Road, San Diego, CA 92121, USA. ask@chemdiv.com

PMID: 16321531
DOI: 10.1016/j.bmcl.2005.11.033

Abstract

A novel potent derivatives of hetaryl imidazoles were described as inhibitors of vascular endothelial growth factor receptor II (VEGFR-2). Several compounds display VEGFR-2 inhibitory activity reaching IC(50)<100 nM in both enzymatic and cellular assays. The compounds also inhibit the related tyrosine kinase, VEGFR-1. By controlling the substitution pattern on the 5-carboxamido functionality, both dual and specific VEGFR-2 thiazoles were identified.

MeSH terms

Imidazoles / chemical synthesis
Imidazoles / chemistry*
Imidazoles / pharmacology*
Inhibitory Concentration 50
Molecular Structure
Structure-Activity Relationship
Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors*
Vascular Endothelial Growth Factor Receptor-1 / metabolism
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

Imidazoles
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2