11�-Hydroxysteroid dehydrogenase type 1 (11�-HSD1) is a reductase converting inactive glucocorticoid hormone cortisone into active glucocorticoid hormone cortisol that regulates glucose and lipid homeostasis. Thus, 11�-HSD1 inhibitors have been explored as potential therapeutics for mainly type 2 diabetes, obesity and dyslipidemia by regulating the concentrations of cortisol. In our research project, we found a weak 11�-HSD1 inhibitory activity in a cyclohexyl acetamide compound. Exploration based on this compound led to a series of adamantyl urea derivatives possessing improved inhibitory potency. We will present the lead generation and further optimization toward our novel 11�-HSD1 inhibitors with nano molar inhibitory activities.

Identification of adamantyl urea derivatives as novel and selective 11�-HSD1 inhibitors

247th National Meeting (2014)

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