Synthesis and structural activity relationship of 11beta-HSD1 inhibitors with novel adamantane replacements

Vince S C Yeh; Ravi Kurukulasuriya; David Madar; Jyoti R Patel; Steven Fung; Katina Monzon; William Chiou; Jiahong Wang; Peer Jacobson; Hing L Sham; J T Link

doi:10.1016/j.bmcl.2006.07.062

Synthesis and structural activity relationship of 11beta-HSD1 inhibitors with novel adamantane replacements

Bioorg Med Chem Lett. 2006 Oct 15;16(20):5408-13. doi: 10.1016/j.bmcl.2006.07.062. Epub 2006 Aug 4.

Authors

Vince S C Yeh¹, Ravi Kurukulasuriya, David Madar, Jyoti R Patel, Steven Fung, Katina Monzon, William Chiou, Jiahong Wang, Peer Jacobson, Hing L Sham, J T Link

Affiliation

¹ Metabolic Disease Research, Abbott Laboratories, 100 Abbott Park Road, AP-10,304B, Abbott Park, IL 60064, USA. [email protected]

PMID: 16890427
DOI: 10.1016/j.bmcl.2006.07.062

Abstract

A series of structurally novel and metabolically stable bridged bicyclic carbocycle and heterocycle adamantane replacements have been synthesized and biologically evaluated. Several of these compounds exhibit excellent human and mouse 11beta-HSD1 potency and 11beta-HSD2 selectivity.

MeSH terms

11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
11-beta-Hydroxysteroid Dehydrogenase Type 2 / antagonists & inhibitors
Adamantane / chemical synthesis*
Adamantane / chemistry
Adamantane / pharmacology*
Animals
Cell Line
Drug Evaluation, Preclinical
Enzyme Activation / drug effects
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
In Vitro Techniques
Mice
Microsomes, Liver / drug effects
Microsomes, Liver / enzymology
Molecular Conformation
Stereoisomerism
Structure-Activity Relationship

Substances

Enzyme Inhibitors
11-beta-Hydroxysteroid Dehydrogenase Type 1
11-beta-Hydroxysteroid Dehydrogenase Type 2
Adamantane