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11β-hydroxysteroid dehydrogenase type 1 inhibitors: a review of recent patents

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Pages 801-825 | Published online: 21 May 2009
 

Abstract

Background: The main components of metabolic syndrome (obesity, insulin resistance, hypertension and dyslipidemia) have become prevalent worldwide, and excess glucocorticoid levels have been implicated in patients with these symptoms. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme involved in glucocorticoid regulation through catalysis of the conversion of inactive cortisone to its active form cortisol. Numerous rodent studies have demonstrated the potential use of 11β-HSD1 inhibitors as treatment for the components of metabolic syndrome and limited clinical data in humans have shown 11β-HSD1 inhibition to improve glucose levels, insulin sensitivity and lipid profiles. Many organizations have been active in the 11β-HSD1 academic and patent literature, and two previous articles from this journal have reviewed disclosures through August 2007. Objective: To summarize the recent patent literature and progress in defining the utility of small molecule 11β-HSD1 inhibitors. Methods: This review covers the recent 11β-HSD1 patent literature and clinical activity ranging from late 2007 through the end of 2008. Results/conclusion: The exploration of 11β-HSD1 inhibitors continues, as a number of structural classes have been reported by several pharmaceutical companies over the past 16 months. Current clinical trials will ultimately shed light on the feasibility of 11β-HSD1 inhibitors as pharmaceutical agents for the various components of metabolic syndrome.

Acknowledgment

The authors thank Jared Cumming for extensive proofreading of this document.

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