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Published on: September 8, 2013
Adamantane 11-beta-HSD-1 inhibitors: Application of an isocyanide multicomponent reaction
Bryan Sorensen1, Jeff Rohde, Jiahong Wang
1Metabolic Disease Research, Abbott, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
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.
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