- The development and SAR of pyrrolidine carboxamide 11beta-HSD1 inhibitors.
The development and SAR of pyrrolidine carboxamide 11beta-HSD1 inhibitors.
Bioorganic & medicinal chemistry letters (2010-04-07)
Hengmiao Cheng, Jacqui Hoffman, Phuong Le, Sajiv K Nair, Stephan Cripps, Jean Matthews, Christopher Smith, Michele Yang, Stan Kupchinsky, Klaus Dress, Martin Edwards, Bridget Cole, Evan Walters, Christine Loh, Jacques Ermolieff, Andrea Fanjul, Ganesh B Bhat, Jocelyn Herrera, Tom Pauly, Natilie Hosea, Genevieve Paderes, Paul Rejto
PMID20363126
ABSTRACT
The design and development of a series of highly selective pyrrolidine carboxamide 11beta-HSD1 inhibitors are described. These compounds including PF-877423 demonstrated potent in vitro activity against both human and mouse 11beta-HSD1 enzymes. In an in vivo assay, PF-877423 inhibited the conversion of cortisone to cortisol. Structure guided optimization effort yielded potent and stable 11beta-HSD1 selective inhibitor 42.
MATERIALS