Discovery and optimization of adamantyl carbamate inhibitors of 11β-HSD1.


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. 
DOI: 10.1016/j.bmcl.2010.08.142


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@article{Tice2010DiscoveryAO, title={Discovery and optimization of adamantyl carbamate inhibitors of 11β-HSD1.}, author={Colin M Tice and Wei Zhao and Paula M Krosky and Barbara A Kruk and Jennifer Berbaum and Judith A. Johnson and Yuri Bukhtiyarov and Reshma Panemangalore and Boyd B. Scott and Yi Zhao and Joseph G Bruno and Lamont Howard and Jennifer Togias and Yuan-Jie Ye and Suresh B. Singh and Brian M. McKeever and Peter Lindblom and Joan Guo and Rong Guo and Herbert Nar and Annette Schuler-Metz and Richard E. Gregg and Katerina Leftheris and Richard K Harrison and Gerard M. McGeehan and Linghang Zhuang and David A. Claremon}, journal={Bioorganic & medicinal chemistry letters}, year={2010}, volume={20 22}, pages={6725-9} }