Adamantane 11-beta-HSD-1 inhibitors: Application of an isocyanide multicomponent reaction.
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.
Sorensen
Bryan
B
Metabolic Disease Research, Abbott, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
Rohde
Jeff
J
Wang
Jiahong
J
Fung
Steven
S
Monzon
Katina
K
Chiou
William
W
Pan
Liping
L
Deng
Xiaoqing
X
Stolarik
DeAnne
D
Frevert
Ernst U
EU
Jacobson
Peer
P
Link
J T
JT
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
D003486:Cyanides; D004791:Enzyme Inhibitors; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000218:Adamantane