1,3-Diaxially Substituted trans-Decalins: Potential Nonsteroidal Human Progesterone Receptor Inhibitors

On the basis of molecular modeling and QSAR analysis of the known human progesterone receptor (hPR) inhibitor Mifepristone (RU-486) and other hPR ligands, a new class of potential nonsteroidal hPR inhibitors was designed. The parent racemic compound 1 was synthesized through an efficient 13-step synthetic pathway. The key constructive steps are a stereoselective epoxide ring opening and the reductive Heck cyclization to form the main framework of (±)-1. The current established flexible synthetic route allows for further chemical diversification.

基于对已知人孕激素受体（hPR）抑制剂米非司酮（RU-486）及其他hPR配体的分子建模与定量构效关系（QSAR）分析，设计出一种新型潜在的甾体非甾体hPR抑制剂。其母体外消旋化合物1通过一条高效的13步合成途径制备而成。关键的构建步骤包括立体选择性的环氧环开环反应以及还原性Heck环化反应，以形成(±)-1的主要骨架。目前建立的灵活合成路线，为进一步的化学多样化提供了可能。