Adamantane 11-beta-HSD-1 inhibitors: Application of an isocyanide multicomponent reaction.

Bryan Sorensen, Jeff Rohde,Jiahong Wang,Steven Fung,Katina Monzon,William Chiou, Liping Pan,Xiaoqing Deng,DeAnne Stolarik,Ernst U Frevert,Peer Jacobson, J T Link

Bioorganic & medicinal chemistry letters（2006）

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摘要

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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