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Discovery and optimization of adamantyl carbamate inhibitors of 11β-HSD1
Colin M Tice1, Wei Zhao, Paula M Krosky
1Vitae Pharmaceuticals, 502 W. Office Center Drive, Fort Washington, PA 19034, USA. ctice@vitaerx.com
Bioorganic & Medicinal Chemistry Letters
|September 25, 2010
Abstract:
Synthesis of 2-adamantyl carbamate derivatives of piperidines and pyrrolidines led to the discovery of 9a with an IC(50) of 15.2 nM against human 11β-HSD1 in adipocytes. Optimization for increased adipocyte potency, metabolic stability and selectivity afforded 11k and 11l, both of which were >25% orally bioavailable in rat.
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