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

被引：60

作者：

Courtney, SM

Hay, PA

Buck, RT

Colville, CS

Phillips, DJ

Scopes, DIC

Pollard, FC

Page, MJ

Bennett, JM

Hircock, ML

McKenzie, EA

Bhaman, M

Felix, R

Stubberfield, CR

Turner, PR

机构：

[1] Celltech R&D Ltd, Dept Oncol, Abingdon OX14 1YS, Oxon, England

[2] Celltech R&D Ltd, Dept Med Chem, Abingdon OX14 1YS, Oxon, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 09期

关键词：

heparanase; angiogenesis; metastasis; beta-glucuronidase; benzoxazole;

D O I：

10.1016/j.bmcl.2005.03.014

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 similar to 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. (c) 2005 Elsevier Ltd. All rights reserved.

引用

收藏

页码：2295 / 2299

页数：5

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