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

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. 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-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 11beta-HSD1 inhibitors as treatment for the components of metabolic syndrome and limited clinical data in humans have shown 11beta-HSD1 inhibition to improve glucose levels, insulin sensitivity and lipid profiles. Many organizations have been active in the 11beta-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 11beta-HSD1 inhibitors.

Methods: This review covers the recent 11beta-HSD1 patent literature and clinical activity ranging from late 2007 through the end of 2008.

Results/conclusion: The exploration of 11beta-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 11beta-HSD1 inhibitors as pharmaceutical agents for the various components of metabolic syndrome.