title: Synthesis and structural activity relationship of 11beta-HSD1 inhibitors with novel adamantane replacements.
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.
authors.affiliation: Metabolic Disease Research, Abbott Laboratories, 100 Abbott Park Road, AP-10,304B, Abbott Park, IL 60064, USA. vince.yeh@abbott.com
authors.forename: Vince S C
authors.initials: VS
authors.lastname: Yeh
authors.forename: Ravi
authors.initials: R
authors.lastname: Kurukulasuriya
authors.forename: David
authors.initials: D
authors.lastname: Madar
authors.forename: Jyoti R
authors.initials: JR
authors.lastname: Patel
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: Peer
authors.initials: P
authors.lastname: Jacobson
authors.forename: Hing L
authors.initials: HL
authors.lastname: Sham
authors.forename: J T
authors.initials: JT
authors.lastname: Link
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000037:antagonists & inhibitors; D000218:Adamantane / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000218:Adamantane