Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1372224 | Bioorganic & Medicinal Chemistry Letters | 2009 | 5 Pages |
Abstract
N-(Pyridin-2-yl) arylsulfonamides are identified as inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), an enzyme that catalyzes the reduction of the glucocorticoid cortisone to cortisol. Dysregulation of glucocorticoids has been implicated in the pathogenesis of diabetes and the metabolic syndrome. In this Letter, we present the development of an initial lead to an efficient ligand with improved physiochemical properties using a deletion strategy. This strategy allowed for further optimization of potency leading to the discovery of the clinical candidate PF-915275.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Michael Siu, Theodore O. Johnson, Yong Wang, Sajiv K. Nair, Wendy D. Taylor, Stephan J. Cripps, Jean J. Matthews, Martin P. Edwards, Thomas A. Pauly, Jacques Ermolieff, Arturo Castro, Natilie A. Hosea, Amy LaPaglia, Andrea N. Fanjul, Jennifer E. Vogel,