| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1374289 | Bioorganic & Medicinal Chemistry Letters | 2010 | 6 Pages |
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.
Graphical abstractThe 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 was carried out to improve metabolic stability for this pyrrolidine carboxamide series.Figure optionsDownload full-size imageDownload as PowerPoint slide
