Jiang Weiqin, Fiordeliso James J, Allan George, Linton Olivia, Tannenbaum Pamela, Xu Jun, Zhu Peifang, Gunnet Joseph, Demarest Keith, Lundeen Scott, Sui Zhihua
Johnson & Johnson Pharmaceutical Research & Development L.L.C., Drug Discovery, 1000 Route 202, Raritan, NJ 08869, USA.
Bioorg Med Chem Lett. 2007 Mar 1;17(5):1471-4. doi: 10.1016/j.bmcl.2006.10.003. Epub 2006 Oct 5.
Mifepristone is a non-selective antagonist of 3-oxosteroid receptors with both abortifacient and anti-diabetic activities. For glucocorticoid receptor (GR) program, we sought an unexplored, synthetically accessible phosphorus-containing steroidal mimetic of mifepristone, suitable for parallel synthesis of analogues. One compound 4a, with high oral bioavailability (59%) in rat, exhibited functional antagonism of GR in oral glucose tolerance test (OGTT). Thus this series of compounds might be potentially useful for the treatment of type II diabetes.
米非司酮是一种3-氧代甾体受体的非选择性拮抗剂，具有堕胎和抗糖尿病活性。对于糖皮质激素受体（GR）项目，我们寻找了一种未被探索的、可通过合成获得的含磷甾体类米非司酮模拟物，适用于类似物的平行合成。一种化合物4a在大鼠中具有高口服生物利用度（59%），在口服葡萄糖耐量试验（OGTT）中表现出GR的功能拮抗作用。因此，这一系列化合物可能对II型糖尿病的治疗具有潜在用途。
