| Literature DB >> 19473839 |
Michael Siu1, 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.
Abstract
N-(Pyridin-2-yl) arylsulfonamides are identified as inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), 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.Entities:
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Year: 2009 PMID： 19473839 DOI： 10.1016/j.bmcl.2009.05.011
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823