11β-hydroxysteroid dehydrogenase type 1 inhibitors as therapeutic agents

11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) plays an essential role in regulating the access of glucocorticoids to nuclear receptors. Chronically elevated levels of glucocorticoids cause obesity, diabetes, cardiovascular disease (the metabolic syndrome) and impairments in memory. Dysregulation of 11 beta-HSD1 has been implicated in all of these disease states. Studies with transgenic mice have demonstrated that overexpression of 11 beta-HSD1 in adipose tissue produces the metabolic syndrome, while knockout of the enzyme produces mice with a cardioprotective phenotype that resist cognitive decline with ageing. Studies with selective 11 beta-HSD1 inhibitors have demonstrated that it is possible to lower plasma glucose and triglyceride levels as well as food intake and the rate of body weight gain. Consequently, 11 beta-HSD1 is an important target for the treatment of the metabolic syndrome and cognitive impairment, with many companies pursuing the development of inhibitors. This patent review focuses on the large number of patents published since 2005.