4-Aryl-1,2,3-triazole: a novel template for a reversible methionine aminopeptidase 2 inhibitor, optimized to inhibit angiogenesis in vivo

  • J Med Chem. 2005 Sep 8;48(18):5644-7. doi: 10.1021/jm050408c.
Lara S Kallander  1 ,  Qing Lu ,  Wenfang Chen ,  Thaddeus Tomaszek ,  Guang Yang ,  David Tew ,  Thomas D Meek ,  Glenn A Hofmann ,  Christina K Schulz-Pritchard ,  Ward W Smith ,  Cheryl A Janson ,  M Dominic Ryan ,  Gui-Feng Zhang ,  Kyung O Johanson ,  Robert B Kirkpatrick ,  Thau F Ho ,  Paul W Fisher ,  Michael R Mattern ,  Randall K Johnson ,  Michael J Hansbury ,  James D Winkler ,  Keith W Ward ,  Daniel F Veber ,  Scott K Thompson
Affiliations
  • 1. GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA. [email protected]
PMID: 16134930 DOI: 10.1021/jm050408c
Abstract

Inhibitors of human methionine Aminopeptidase type 2 (hMetAP2) are of interest as potential treatments for Cancer. A new class of small molecule reversible inhibitors of hMetAP2 was discovered and optimized, the 4-aryl-1,2,3-triazoles. Compound 24, a potent inhibitor of cobalt-activated hMetAP2, also inhibits human and mouse endothelial cell growth. Using a mouse matrigel model, this reversible hMetAP2 inhibitor was also shown to inhibit angiogenesis in vivo.