edoc

Synthesis of novel 3-amino and 29-hydroxamic acid derivatives of glycyrrhetinic acid as selective 11?-hydroxysteroid dehydrogenase 2 inhibitors

Stanetty, Christian and Czollner, Laszlo and Koller, Iris and Shah, Priti and Gaware, Rawindra and Cunha, Thierry Da and Odermatt, Alex and Jordis, Ulrich and Kosma, Paul and Classen-Houben, Dirk. (2010) Synthesis of novel 3-amino and 29-hydroxamic acid derivatives of glycyrrhetinic acid as selective 11?-hydroxysteroid dehydrogenase 2 inhibitors. Bioorganic & medicinal chemistry, Vol. 18, H. 21. pp. 7522-7541.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A5841135

Downloads: Statistics Overview

Abstract

Glycyrrhetinic acid, the metabolite of the natural product glycyrrhizin, is a well known nonselective inhibitor of 11?-hydroxysteroid dehydrogenase (11?-HSD) type 1 and type 2. Whereas inhibition of 11?-HSD1 is currently under consideration for treatment of metabolic diseases, such as obesity and diabetes, 11?-HSD2 inhibitors may find therapeutic applications in chronic inflammatory diseases and certain forms of cancer. So far, no selective 11?-HSD2 inhibitor has been developed and neither animal studies nor clinical trials have been reported based on 11?-HSD2 inhibition. Starting from the lead compound glycyrrhetinic acid, novel triterpene type derivatives were synthesized and analyzed for their biological activity against overexpressed human 11?-HSD1 and 11?-HSD2 in cell lysates. Several hydroxamic acid derivatives showed high selectivity for 11?-HSD2. The most potent and selective compound is active against human 11?-HSD2 in the low nanomolar range with a 350-fold selectivity over human 11?-HSD1.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molecular and Systems Toxicology (Odermatt)
UniBasel Contributors:Odermatt, Alex
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Pergamon
ISSN:0968-0896
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:14 Sep 2012 07:17
Deposited On:14 Sep 2012 06:37

Repository Staff Only: item control page