Furanyl-1,3-thiazol-2-yl and benzoxazol-5-yl acetic acid derivatives: novel classes of heparanase inhibitor

  • Bioorg Med Chem Lett. 2005 May 2;15(9):2295-9. doi: 10.1016/j.bmcl.2005.03.014.
Stephen M Courtney  1 ,  Philip A Hay ,  Richard T Buck ,  Claire S Colville ,  David J Phillips ,  David I C Scopes ,  Faye C Pollard ,  Martin J Page ,  James M Bennett ,  Margaret L Hircock ,  Edward A McKenzie ,  Maina Bhaman ,  Robert Felix ,  Colin R Stubberfield ,  Paul R Turner
Affiliations
  • 1. Department of Medicinal Chemistry, Celltech R&D Ltd, 4-10 The Quadrant, Abingdon Science Park, Abingdon, Oxfordshire OX14 4YS, UK.
PMID: 15837312 DOI: 10.1016/j.bmcl.2005.03.014
Abstract

Using a furanylthiazole acetic acid as a starting point, a novel series of benzoxazol-5-yl acetic acid derivatives have been identified as heparanase inhibitors. Several compounds possess an IC50 of approximately 200 nM against heparanase, for example, trans 2-[4-[3-(3,4-dichlorophenylamino)-3-oxo-1-propenyl]-2-fluorophenyl]benzoxazol-5-yl acetic acid (16e). Several of the compounds show anti-angiogenic properties. Improvement to the DMPK profile of compounds has provided compounds of potential use in in vivo models.

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