Parallel strategies for the preparation and selection of liver-targeted glucocorticoid receptor antagonists.
Basic Information
ID: ALA1143774
Journal: Bioorg Med Chem Lett
Title: Parallel strategies for the preparation and selection of liver-targeted glucocorticoid receptor antagonists.
Authors: Backes BJ, Hamilton GL, Nguyen P, Wilcox D, Fung S, Wang J, Grynfarb M, Goos-Nilsson A, Jacobson PB, von Geldern TW.
Abstract: 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.
CiteXplore: 17070047
DOI: 10.1016/j.bmcl.2006.10.001
Patent ID: ┄