title: Structure based design of 11β-HSD1 inhibitors.
abstract: Controlling elevated tissue-specific levels of cortisol may provide a novel therapeutic approach for treating metabolic syndrome. This concept has spurred large scale medicinal chemistry efforts in the pharmaceutical industry for the design of 11β-HSD1 inhibitors. High resolution X-ray crystal structures of inhibitors in complex with the enzyme have facilitated the structure-based design of diverse classes of molecules. A summary of binding modes, trends in structure-activity relationships, and the pharmacodynamic data of inhibitors from each class is presented.
authors.affiliation: Vitae Pharmaceuticals, 502 W. Office Center Drive, Fort Washington, PA 19034, USA. ssingh@vitaerx.com
authors.forename: Suresh
authors.initials: S
authors.lastname: Singh
authors.forename: Colin
authors.initials: C
authors.lastname: Tice
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002986:Clinical Trials as Topic / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1