Discovery of novel, potent benzamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) exhibiting oral activity in an enzyme inhibition ex vivo model.
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Julian LD, Wang Z, Bostick T, Caille S, Choi R, DeGraffenreid M, Di Y, He X, Hungate RW, Jaen JC, Liu J, Monshouwer M, McMinn D, Rew Y, Sudom A, Sun D, Tu H, Ursu S, Walker N, Yan X, Ye Q, Powers JP
Discovery of novel, potent benzamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) exhibiting oral activity in an enzyme inhibition ex vivo model.
J Med Chem. 2008 Jul 10;51(13):3953-60. doi: 10.1021/jm800310g. Epub 2008 Jun 14.
- PubMed ID
- 18553955 [ View in PubMed]
- Abstract
We report the discovery of potent benzamide inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1). The optimization and correlation of in vitro and in vivo metabolic stability will be described. Through modifications to our initial lead 2, we discovered pyridyl compound 13. This compound has a favorable pharmacokinetic profile across three species and showed a dose-dependent decrease in adipose 11beta-HSD1 activity in a monkey ex vivo pharmacodynamic model.
DrugBank Data that Cites this Article
- Polypeptides
Name UniProt ID Corticosteroid 11-beta-dehydrogenase isozyme 1 P28845 Details - Binding Properties