Development of 11β-HSD1 inhibitors for the treatment
of metabolic syndrome

V.V. Lipson^1,2, L.L. Zamigajlo³, O.N. Petrova³

¹ Antidiabetic Drug Laboratory, State Institution «V.Ya. Danilevsky Institute for Endocrine Pathology Problems» of the Academy of Medical Sciences of Ukraine
Artema St., 10, 61002, Kharkov, Ukraine

^1,2 V.N. Karazin Kharkov National University, Organic Chemistry Department
Svobody Sq., 4, 61077, Kharkov, Ukraine

³ State Scientific Institution «Institute for Single Crystals» of the National Academy of Sciences of Ukraine Lenina Prosp. 60, 61001, Kharkov, Ukraine

Summury. 11β-Hydroxysteroid dehydrogenase type I (11β-HSD1) is the enzyme that converts inactive 11-ketoglucocorticoids into active 11β-hydroxy-forms in metabolically relevant tissues such as the liver, adipose tissue and skeletal muscles. Chronically elevated local glucocorticoid action as a result of increased 11β-HSD1 activity is associated with metabolic syndrome, obesity, insulin resistance, type 2 diabetes mellitus and cardiovascular complications. Inhibition of 11β-HSD1 has been proposed as a strategy to suppress glucocorticoid action in tissue-specific manner. A large variety of 11β-HSD1 inhibitors from different series of nitrogen containing heterocycles are now under investigation to treat type 2 diabetes and obesity.

Keywords: 11β-hydroxysteroid dehydrogenase, cortisol, metabolic syndrome, obesity, drug development.