Adamantyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1

Steven Olson; Susan D Aster; Kai Brown; Linda Carbin; Donald W Graham; Anne Hermanowski-Vosatka; Cheryl B LeGrand; Steven S Mundt; Michael A Robbins; James M Schaeffer; Llnon H Slossberg; Michael J Szymonifka; Rolf Thieringer; Samuel D Wright; James M Balkovec

doi:10.1016/j.bmcl.2005.06.040

Adamantyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1

Bioorg Med Chem Lett. 2005 Oct 1;15(19):4359-62. doi: 10.1016/j.bmcl.2005.06.040.

Authors

Steven Olson¹, Susan D Aster, Kai Brown, Linda Carbin, Donald W Graham, Anne Hermanowski-Vosatka, Cheryl B LeGrand, Steven S Mundt, Michael A Robbins, James M Schaeffer, Llnon H Slossberg, Michael J Szymonifka, Rolf Thieringer, Samuel D Wright, James M Balkovec

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. [email protected]

PMID: 16039856
DOI: 10.1016/j.bmcl.2005.06.040

Abstract

Adamantyl triazoles were identified as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). They are active both in in vitro and in in vivo pharmacodynamic models. The synthesis and structure-activity relationships of these inhibitors are presented.

MeSH terms

11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
Adamantane / chemical synthesis
Adamantane / pharmacokinetics
Adamantane / pharmacology
Animals
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacokinetics
Enzyme Inhibitors / pharmacology
Humans
Inhibitory Concentration 50
Metabolic Syndrome / drug therapy
Mice
Pharmacokinetics
Structure-Activity Relationship
Triazoles / chemical synthesis*
Triazoles / pharmacokinetics
Triazoles / pharmacology

Substances

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