Chen Liqiang, Wilson Daniel J, Labello Nicholas P, Jayaram Hiremagalur N, Pankiewicz Krzysztof W
Center for Drug Design, Academic Health Center, University of Minnesota, 516 Delaware Street S.E., Minneapolis, MN 55455, USA.
Bioorg Med Chem. 2008 Oct 15;16(20):9340-5. doi: 10.1016/j.bmc.2008.08.062. Epub 2008 Aug 29.
Mycophenolic acid (MPA), a clinically used immunosuppressant, is extensively metabolized into an inactive C7-glucuronide and removed from circulation. To circumvent the metabolic liability imposed by the C7-hydroxyl group, we have designed a series of hybrid MPA analogs based on the pharmacophores present in MPA and new generations of inosine monophosphate dehydrogenase (IMPDH) inhibitors. The synthesis of MPA analogs has been accomplished by an allylic substitution of a common lactone. Biological evaluations of these analogs and a preliminary structure-activity relationship (SAR) are presented.
霉酚酸（MPA）是一种临床使用的免疫抑制剂，可广泛代谢为无活性的C7-葡萄糖醛酸苷并从循环中清除。为了规避C7-羟基带来的代谢负担，我们基于MPA中存在的药效基团和新一代肌苷单磷酸脱氢酶（IMPDH）抑制剂设计了一系列杂合MPA类似物。MPA类似物的合成已通过一种常见内酯的烯丙基取代反应完成。本文介绍了这些类似物的生物学评价和初步的构效关系（SAR）。
