The discovery of azepane sulfonamides as potent 11beta-HSD1 inhibitors

Santhosh F Neelamkavil; Craig D Boyle; Samuel Chackalamannil; William J Greenlee; Lili Zhang; Giuseppe Terracina

doi:10.1016/j.bmcl.2009.07.003

The discovery of azepane sulfonamides as potent 11beta-HSD1 inhibitors

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4563-5. doi: 10.1016/j.bmcl.2009.07.003. Epub 2009 Jul 8.

Authors

Santhosh F Neelamkavil¹, Craig D Boyle, Samuel Chackalamannil, William J Greenlee, Lili Zhang, Giuseppe Terracina

Affiliation

¹ Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. [email protected]

PMID: 19625185
DOI: 10.1016/j.bmcl.2009.07.003

Abstract

Discovery of a series of azepine sulfonamides as potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is described. SAR studies at the 4-position of the azepane ring have resulted in the discovery of a very potent compound 30 which has an 11beta-HSD1 IC(50) of 3.0nM.

MeSH terms

11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
Animals
Anti-Inflammatory Agents / chemical synthesis
Anti-Inflammatory Agents / chemistry*
Anti-Inflammatory Agents / pharmacology
Azepines / chemical synthesis*
Azepines / chemistry*
Azepines / pharmacology
Drug Discovery
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Humans
Mice
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry*
Sulfonamides / pharmacology

Substances

Anti-Inflammatory Agents
Azepines
Enzyme Inhibitors
Sulfonamides
11-beta-Hydroxysteroid Dehydrogenase Type 1