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

被引：69

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 [生物化学与分子生物学]; 081704 [应用化学];

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.

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页码：4439 / 4457

页数：19

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