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


CONCLUSIONS
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.
Boyle
Craig D
CD
CNS and CV/Metabolic Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-2-2545, Kenilworth, NJ 07033-1300, USA. craig.boyle@spcorp.com
Kowalski
Timothy J
TJ
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D010330:Patents as Topic
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D008055:Lipids; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1