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

  • Bioorg Med Chem Lett. 2006 Dec 1;16(23):5958-62. doi: 10.1016/j.bmcl.2006.08.129.
Bryan Sorensen  1 ,  Jeff Rohde ,  Jiahong Wang ,  Steven Fung ,  Katina Monzon ,  William Chiou ,  Liping Pan ,  Xiaoqing Deng ,  DeAnne Stolarik ,  Ernst U Frevert ,  Peer Jacobson ,  J T Link
Affiliations
  • 1. Metabolic Disease Research, Abbott, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
PMID: 16996734 DOI: 10.1016/j.bmcl.2006.08.129
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.