1. The development and SAR of pyrrolidine carboxamide 11β-HSD1 inhibitors
- Author
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Cheng, Hengmiao, Hoffman, Jacqui, Le, Phuong, Nair, Sajiv K., Cripps, Stephan, Matthews, Jean, Smith, Christopher, Yang, Michele, Kupchinsky, Stan, Dress, Klaus, Edwards, Martin, Cole, Bridget, Walters, Evan, Loh, Christine, Ermolieff, Jacques, Fanjul, Andrea, Bhat, Ganesh B., Herrera, Jocelyn, Pauly, Tom, and Hosea, Natilie
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PYRROLIDINE , *ENZYME inhibitors , *CORTISONE , *ENZYME activation , *DIABETES - Abstract
Abstract: The design and development of a series of highly selective pyrrolidine carboxamide 11β-HSD1 inhibitors are described. These compounds including PF-877423 demonstrated potent in vitro activity against both human and mouse 11β-HSD1 enzymes. In an in vivo assay, PF-877423 inhibited the conversion of cortisone to cortisol. Structure guided optimization effort yielded potent and stable 11β-HSD1 selective inhibitor 42. [Copyright &y& Elsevier]
- Published
- 2010
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