title: Discovery of 4-heteroarylbicyclo[2.2.2]octyltriazoles as potent and selective inhibitors of 11beta-HSD1: novel therapeutic agents for the treatment of metabolic syndrome.
abstract: Replacement of the pentyl chain on our original bicyclo[2.2.2]octyltriazole leads 1 and 2 has led to the discovery that heteroaryl substituted bicyclo[2.2.2]octyltriazoles are potent and selective 11beta-hydroxysteroid dehydrogenase type I (11beta-HSD1) inhibitors with excellent pharmacokinetic profiles.
authors.affiliation: Department of Medicinal Chemistry, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. xin_gu@merck.com
authors.forename: Xin
authors.initials: X
authors.lastname: Gu
authors.forename: Jasminka
authors.initials: J
authors.lastname: Dragovic
authors.forename: Gloria C
authors.initials: GC
authors.lastname: Koo
authors.forename: Sam L
authors.initials: SL
authors.lastname: Koprak
authors.forename: Cheryl
authors.initials: C
authors.lastname: LeGrand
authors.forename: Steven S
authors.initials: SS
authors.lastname: Mundt
authors.forename: Kashmira
authors.initials: K
authors.lastname: Shah
authors.forename: Marty S
authors.initials: MS
authors.lastname: Springer
authors.forename: Eugene Y
authors.initials: EY
authors.lastname: Tan
authors.forename: Rolf
authors.initials: R
authors.lastname: Thieringer
authors.forename: Anne
authors.initials: A
authors.lastname: Hermanowski-Vosatka
authors.forename: Hratch J
authors.initials: HJ
authors.lastname: Zokian
authors.forename: James M
authors.initials: JM
authors.lastname: Balkovec
authors.forename: Sherman T
authors.initials: ST
authors.lastname: Waddell
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D024821:Metabolic Syndrome / Q000188:drug therapy*; D051379:Mice; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*
chemical_list: D004791:Enzyme Inhibitors; D014230:Triazoles; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1