Discovery of potent and selective inhibitors of 11beta-HSD1 for the treatment of metabolic syndrome

Steven Richards; Bryan Sorensen; Hwan-Soo Jae; Marty Winn; Yixian Chen; Jiahong Wang; Steven Fung; Katina Monzon; Ernst U Frevert; Peer Jacobson; Hing Sham; J T Link

doi:10.1016/j.bmcl.2006.09.035

Discovery of potent and selective inhibitors of 11beta-HSD1 for the treatment of metabolic syndrome

Bioorg Med Chem Lett. 2006 Dec 15;16(24):6241-5. doi: 10.1016/j.bmcl.2006.09.035. Epub 2006 Sep 26.

Authors

Steven Richards¹, Bryan Sorensen, Hwan-Soo Jae, Marty Winn, Yixian Chen, Jiahong Wang, Steven Fung, Katina Monzon, Ernst U Frevert, Peer Jacobson, Hing Sham, J T Link

Affiliation

¹ Metabolic Disease Research, GPRD, Abbott Laboratories, 100 Abbott Park Rd., Abbott Park, IL 60064, USA. Steven.Richards@abbott.com

PMID: 17000111
DOI: 10.1016/j.bmcl.2006.09.035

Abstract

High throughput screening efforts have identified a novel class of dichloroaniline amide 11beta-HSD1 inhibitors. SAR studies initiated from dichloroaniline 4 focused on retaining the potency and selectivity profile of the lead.

MeSH terms

11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
Carbenoxolone / chemistry
Carbenoxolone / pharmacology
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Enzyme Inhibitors / therapeutic use
Humans
Metabolic Syndrome / drug therapy*
Molecular Conformation
Piperazines / chemistry
Piperazines / pharmacology
Sulfonamides / chemistry
Sulfonamides / pharmacology
Thiazoles / chemistry
Thiazoles / pharmacology

Substances

3-chloro-2-methyl-N-(4-(2-(4-methyl-1-piperazinyl)-2-oxoethyl)-1,3-thiazol-2-yl)benzenesulfonamide
Enzyme Inhibitors
Piperazines
Sulfonamides
Thiazoles
11-beta-Hydroxysteroid Dehydrogenase Type 1
Carbenoxolone