Backes Bradley J, Hamilton Gregory L, Nguyen Phong, Wilcox Denise, Fung Steven, Wang Jiahong, Grynfarb Marlena, Goos-Nilsson Annika, Jacobson Peer B, von Geldern Thomas W
Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6099, USA.
Bioorg Med Chem Lett. 2007 Jan 1;17(1):40-4. doi: 10.1016/j.bmcl.2006.10.001. Epub 2006 Oct 5.
Libraries of mifepristone analogs, MP-Acids, were designed and synthesized to increase the chances of identifying GR antagonists that possess liver-selective pharmacological profiles. MP-Acids were uniformly potent GR antagonists in binding and in cell-based functional assays. A high throughput pharmacokinetic selection strategy that employs the cassette dosing of MP-Acids was developed to identify liver-targeting compounds. Thus, resource-intensive in vivo assays to measure liver-selective pharmacology were enriched with GR antagonists that achieve high concentrations in the liver.
设计并合成了米非司酮类似物库（MP-酸），以增加鉴定具有肝脏选择性药理学特征的糖皮质激素受体（GR）拮抗剂的机会。在结合实验和基于细胞的功能实验中，MP-酸均为强效GR拮抗剂。开发了一种采用MP-酸盒式给药的高通量药代动力学筛选策略，以鉴定靶向肝脏的化合物。因此，用于测量肝脏选择性药理学的资源密集型体内实验中加入了能在肝脏中达到高浓度的GR拮抗剂。
