Zydus Research Centre, Sarkhej-Bavla N.H. 8A Moraiya, Ahmedabad 382210, India.
Bioorg Med Chem Lett. 2012 Sep 15;22(18):5857-62. doi: 10.1016/j.bmcl.2012.07.078. Epub 2012 Jul 31.
Series of benzyl-phenoxybenzyl amino-phenyl acid derivatives (8a-q) are reported as non-steroidal GR antagonist. Compound 8g showed excellent h-GR binding and potent antagonistic activity (in vitro). The lead compound 8g exhibited significant oral antidiabetic and antihyperlipidemic effects (in vivo), along with liver selectivity. These preliminary results confirm discovery of potent and liver selective passive GR antagonist for the treatment of T2DM.
报道了一系列苯甲基-苯氧基苯甲基氨基-苯基酸衍生物（8a-q）作为非甾体类 GR 拮抗剂。化合物 8g 表现出优异的 h-GR 结合和强大的拮抗活性（体外）。先导化合物 8g 表现出显著的口服抗糖尿病和抗高血脂作用（体内），同时具有肝脏选择性。这些初步结果证实了发现强效和肝脏选择性的被动 GR 拮抗剂用于治疗 T2DM。
