title: Discovery of adamantane ethers as inhibitors of 11beta-HSD-1: Synthesis and biological evaluation.
abstract: A novel class of adamantane ethers 11beta-hydroxysteroid hydrogenase type I inhibitors has been discovered. These compounds have excellent HSD-1 potency and selectivity against HSD-2. The structure-activity relationships, selectivity, metabolism, PK, ex vivo pharmacodynamic data, and an X-ray crystal structure of one of these inhibitors bound to h-HSD-1 are discussed.
authors.affiliation: Global Pharmaceutical Research & Development, Abbott Laboratories, R43G, AP52, 200 Abbott Park Road, Abbott Park, IL-60064-6217, USA. jyoti.patel@abbott.com
authors.forename: Jyoti R
authors.initials: JR
authors.lastname: Patel
authors.forename: Qi
authors.initials: Q
authors.lastname: Shuai
authors.forename: Jurgen
authors.initials: J
authors.lastname: Dinges
authors.forename: Marty
authors.initials: M
authors.lastname: Winn
authors.forename: Marina
authors.initials: M
authors.lastname: Pliushchev
authors.forename: Steven
authors.initials: S
authors.lastname: Fung
authors.forename: Katina
authors.initials: K
authors.lastname: Monzon
authors.forename: William
authors.initials: W
authors.lastname: Chiou
authors.forename: Jiahong
authors.initials: J
authors.lastname: Wang
authors.forename: Liping
authors.initials: L
authors.lastname: Pan
authors.forename: Seble
authors.initials: S
authors.lastname: Wagaw
authors.forename: Kenneth
authors.initials: K
authors.lastname: Engstrom
authors.forename: Francis A
authors.initials: FA
authors.lastname: Kerdesky
authors.forename: Kenton
authors.initials: K
authors.lastname: Longenecker
authors.forename: Russell
authors.initials: R
authors.lastname: Judge
authors.forename: Wenying
authors.initials: W
authors.lastname: Qin
authors.forename: Hovis M
authors.initials: HM
authors.lastname: Imade
authors.forename: Deanne
authors.initials: D
authors.lastname: Stolarik
authors.forename: David W A
authors.initials: DW
authors.lastname: Beno
authors.forename: Michael
authors.initials: M
authors.lastname: Brune
authors.forename: Linda E
authors.initials: LE
authors.lastname: Chovan
authors.forename: Hing L
authors.initials: HL
authors.lastname: Sham
authors.forename: Peer
authors.initials: P
authors.lastname: Jacobson
authors.forename: J T
authors.initials: JT
authors.lastname: Link
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D000478:Alkylation; D000818:Animals; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004987:Ethers / Q000138:chemical synthesis / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D007202:Indicators and Reagents; D051379:Mice; D018345:Mice, Knockout; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D008958:Models, Molecular
chemical_list: D004791:Enzyme Inhibitors; D004987:Ethers; D007202:Indicators and Reagents; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D000218:Adamantane