Novel 18β-glycyrrhetinic acid analogues as potent and selective inhibitors of 11β-hydroxysteroid dehydrogenases

被引：56
|
作者：
Su, XD
Lawrence, H
Ganeshapillai, D
Cruttenden, A
Purohit, A
Reed, MJ
Vicker, N
Potter, BVL [1 ]
机构：
[1] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England
[2] Univ Bath, Sterix Ltd, Bath BA2 7AY, Avon, England
[3] Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, Sch Med, Sterix Ltd, London W2 1NY, England
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2004年 / 12卷 / 16期
关键词：
D O I：
10.1016/j.bmc.2004.06.008
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Extensive structural modifications to the 18beta-glycyrrhetinic acid template are described and their effects on the SAR of the 11beta-hydroxysteroid dehydrogenase isozymes type 1 and 2 from the rat are investigated. Isoform selective inhibitors have been discovered and compound 7 N-(2-hydroxyethyl)-3beta-hydroxy-11-oxo-18beta-olean-12-en-30-oic acid amide is highlighted as a very potent selective inhibitor of 11beta-hydroxysteroid dehydrogenase 2 with an IC50 = 4 pM. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4439 / 4457
页数：19
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