11�-hydroxysteroid dehydrogenase type 1 (11�-HSD1) is the reductase converting inactive glucocorticoid hormone cortisone to active glucocorticoid hormone cortisol. 11�-HSD1 inhibitor has been explored as potential therapeutics, such as type 2 diabetes, obesity and dyslipidemia by regulating the amount of cortisol. In our 11�-HSD1 inhibitor project, we found a novel aminopyrazoleamide derivative as a lead compound. The further lead optimization study gave DSP-0011 which exhibited IC50 values of 5.2, 4.2 and 10.3 nM, respectively, for human, mouse and rat 11�-HSD1 and presented good pharmacokinetic and safety profiles.

Discovery of a novel selective 11�-HSD1 inhibitor DSP-0011

246th National Meeting (2013)

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