title: Adamantane 11-beta-HSD-1 inhibitors: Application of an isocyanide multicomponent reaction.
abstract: A series of potent and selective adamantane aminoamide 11-beta-HSD-1 inhibitors has been optimized. Chemically these studies were expedited by utilizing readily obtained amino acids as starting materials or an isocyanide multicomponent reaction. Structure-activity relationship studies resulted in the discovery of dual human and mouse 11-beta-HSD-1 potent and selective inhibitors like adamantane 11 and related compounds with high metabolic stability and robust pharmacokinetic profiles.
authors.affiliation: Metabolic Disease Research, Abbott, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Sorensen
authors.forename: Jeff
authors.initials: J
authors.lastname: Rohde
authors.forename: Jiahong
authors.initials: J
authors.lastname: Wang
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: Liping
authors.initials: L
authors.lastname: Pan
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Deng
authors.forename: DeAnne
authors.initials: D
authors.lastname: Stolarik
authors.forename: Ernst U
authors.initials: EU
authors.lastname: Frevert
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* / Q000378:metabolism; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000218:Adamantane / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D003486:Cyanides / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D003486:Cyanides; D004791:Enzyme Inhibitors; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000218:Adamantane