2. Academic Validation
  3. 3,4-Disubstituted isothiazoles: novel potent inhibitors of VEGF receptors 1 and 2

3,4-Disubstituted isothiazoles: novel potent inhibitors of VEGF receptors 1 and 2

  • Bioorg Med Chem Lett. 2009 Feb 15;19(4):1195-8. doi: 10.1016/j.bmcl.2008.12.078.
Alexander S Kiselyov 1,  Marina Semenova,  Victor V Semenov
Affiliations

Affiliation

  • 1 deCODE, 2501 Davey Road, Woodridge, IL 60616, USA. akiselyov@decode.com
PMID: 19124243 DOI: 10.1016/j.bmcl.2008.12.078
Abstract

Novel derivatives of isothiazoles are described as potent ATP-competitive inhibitors of vascular endothelial growth factor receptors I and II (VEGFR-1/2). A number of compounds exhibited VEGFR-2 inhibitory activity comparable to that of Vatalanib in both HTRF enzymatic and cellular assays. Several derivatives featuring bulky meta-substituents in the amide portion of the molecule displayed 4- to 8-fold specificity for VEGFR-2 versus VEGFR-1. Active molecules also showed high intrinsic permeability (> 30 x 10(-5) cm/min) across Caco-2 cell monolayer.

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