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

  • Bioorg Med Chem. 2004 Aug 15;12(16):4439-57. doi: 10.1016/j.bmc.2004.06.008.
Xiangdong Su  1 ,  Harshani Lawrence ,  Dharshini Ganeshapillai ,  Adrian Cruttenden ,  Atul Purohit ,  Michael J Reed ,  Nigel Vicker ,  Barry V L Potter
Affiliations
  • 1. Medicinal Chemistry, Department of Pharmacy and Pharmacology and Sterix Ltd, University of Bath, Bath BA2 7AY, UK.
PMID: 15265495 DOI: 10.1016/j.bmc.2004.06.008
Abstract

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 IC(50) = 4pM.

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