title: Phenylcyclobutyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I.
abstract: 3-(Phenylcyclobutyl)-1,2,4-triazoles were identified as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). These were active both in vitro and in an in vivo mouse pharmacodynamic (PD) model. Fluorine substitution of the cyclobutane ring improved the pharmacokinetic profile significantly. The synthesis and structure-activity relationships are presented.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. yuping_zhu@merck.com
authors.forename: Yuping
authors.initials: Y
authors.lastname: Zhu
authors.forename: Steven H
authors.initials: SH
authors.lastname: Olson
authors.forename: Donald
authors.initials: D
authors.lastname: Graham
authors.forename: Gool
authors.initials: G
authors.lastname: Patel
authors.forename: Anne
authors.initials: A
authors.lastname: Hermanowski-Vosatka
authors.forename: Steven
authors.initials: S
authors.lastname: Mundt
authors.forename: Kashmira
authors.initials: K
authors.lastname: Shah
authors.forename: Marty
authors.initials: M
authors.lastname: Springer
authors.forename: Rolf
authors.initials: R
authors.lastname: Thieringer
authors.forename: Samuel
authors.initials: S
authors.lastname: Wright
authors.forename: Jianying
authors.initials: J
authors.lastname: Xiao
authors.forename: Hratch
authors.initials: H
authors.lastname: Zokian
authors.forename: Jasminka
authors.initials: J
authors.lastname: Dragovic
authors.forename: James M
authors.initials: JM
authors.lastname: Balkovec
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D000284:Administration, Oral; D000818:Animals; D020650:Combinatorial Chemistry Techniques; D003348:Cortisone / Q000032:analysis / Q000097:blood; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000097:blood; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D014230:Triazoles; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D003348:Cortisone; D006854:Hydrocortisone