beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action

Jason Xiang; Manus Ipek; Vipin Suri; May Tam; Yuzhe Xing; Nelson Huang; Yanling Zhang; James Tobin; Tarek S Mansour; John McKew

doi:10.1016/j.bmc.2007.04.035

beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action

Bioorg Med Chem. 2007 Jul 1;15(13):4396-405. doi: 10.1016/j.bmc.2007.04.035. Epub 2007 Apr 25.

Authors

Jason Xiang¹, Manus Ipek, Vipin Suri, May Tam, Yuzhe Xing, Nelson Huang, Yanling Zhang, James Tobin, Tarek S Mansour, John McKew

Affiliation

¹ Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, MA 02140, USA. jxiang@wyeth.com

PMID: 17490884
DOI: 10.1016/j.bmc.2007.04.035

Abstract

The design, synthesis, and biological evaluation of beta-keto sulfones as 11beta-HSD1 inhibitors and the mechanism of inhibition are described here. This class of compounds is not active against 11beta-HSD2 and therefore may have therapeutic potential for metabolic syndrome and type 2 diabetes.

MeSH terms

11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
Alkylation
Animals
CHO Cells
Cricetinae
Cricetulus
Electrochemistry
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Indicators and Reagents
Ketones / chemical synthesis*
Ketones / pharmacology*
Solvents
Structure-Activity Relationship
Sulfones / chemical synthesis*
Sulfones / pharmacology*

Substances

Enzyme Inhibitors
Indicators and Reagents
Ketones
Solvents
Sulfones
11-beta-Hydroxysteroid Dehydrogenase Type 1