Sorensen Bryan, Rohde Jeff, Wang Jiahong, Fung Steven, Monzon Katina, Chiou William, Pan Liping, Deng Xiaoqing, Stolarik DeAnne, Frevert Ernst U, Jacobson Peer, Link J T
Metabolic Disease Research, Abbott, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
Bioorg Med Chem Lett. 2006 Dec 1;16(23):5958-62. doi: 10.1016/j.bmcl.2006.08.129. Epub 2006 Sep 25.
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.
一系列强效且具选择性的金刚烷氨基酰胺11-β-羟基类固醇脱氢酶-1（11-beta-HSD-1）抑制剂已得到优化。在化学方面，通过使用容易获得的氨基酸作为起始原料或异腈多组分反应，这些研究得以加速推进。构效关系研究促成了对人源和鼠源双重11-β-羟基类固醇脱氢酶-1强效且具选择性抑制剂的发现，如金刚烷11及相关化合物，它们具有高代谢稳定性和良好的药代动力学特征。
