title: Novel 18beta-glycyrrhetinic acid analogues as potent and selective inhibitors of 11beta-hydroxysteroid dehydrogenases.
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.
authors.affiliation: Medicinal Chemistry, Department of Pharmacy and Pharmacology and Sterix Ltd, University of Bath, Bath BA2 7AY, UK.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Su
authors.forename: Harshani
authors.initials: H
authors.lastname: Lawrence
authors.forename: Dharshini
authors.initials: D
authors.lastname: Ganeshapillai
authors.forename: Adrian
authors.initials: A
authors.lastname: Cruttenden
authors.forename: Atul
authors.initials: A
authors.lastname: Purohit
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Reed
authors.forename: Nigel
authors.initials: N
authors.lastname: Vicker
authors.forename: Barry V L
authors.initials: BV
authors.lastname: Potter
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000037:antagonists & inhibitors*; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats
chemical_list: D004791:Enzyme Inhibitors; C496799:N-(2-hydroxyethyl)-3beta-hydroxy-11-oxo-18beta-olean-12-en-30-oic acid amide; D009828:Oleanolic Acid; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D006034:Glycyrrhetinic Acid