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

Authors :
Tice, Colin M.
Zhao, Wei
Krosky, Paula M.
Kruk, Barbara A.
Berbaum, Jennifer
Johnson, Judith A.
Bukhtiyarov, Yuri
Panemangalore, Reshma
Scott, Boyd B.
Zhao, Yi
Bruno, Joseph G.
Howard, Lamont
Togias, Jennifer
Ye, Yuan-Jie
Singh, Suresh B.
McKeever, Brian M.
Lindblom, Peter R.
Guo, Joan
Guo, Rong
Nar, Herbert
Source :
Bioorganic & Medicinal Chemistry Letters. Nov2010, Vol. 20 Issue 22, p6725-6729. 5p.
Publication Year :
2010

Abstract

Abstract: Synthesis of 2-adamantyl carbamate derivatives of piperidines and pyrrolidines led to the discovery of 9a with an IC50 of 15.2nM 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. [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
0960894X
Volume :
20
Issue :
22
Database :
Academic Search Index
Journal :
Bioorganic & Medicinal Chemistry Letters
Publication Type :
Academic Journal
Accession number :
54482668
Full Text :
https://doi.org/10.1016/j.bmcl.2010.08.142