Inducing oligodendrocyte progenitor cell (OPC) differentiation is a novel therapeutic strategy for the treatment of demyelinating diseases such as multiple sclerosis (MS). In the preceding article, we detailed the discovery of compound 1, a potent inducer of OPC differentiation possessing a characteristic spiroindoline structure. Also, we found that N-methylation and des-carbonyl compound 1 (4) led to a loss in potency. Herein, we describe our investigations of a conformation-based hypothesis for OPC differentiation activity based on the preferred conformation of the spiro core, and further structure–activity relationship (SAR) exploration led to the identification of 6-CF₃ derivative 8, which was more potent compared to compound 1.

诱导少突胶质祖细胞（OPC）的分化是一种新型的治疗策略，用于治疗多发性硬化（MS）等脱髓鞘疾病。在上一篇文章中，我们详细介绍了化合物1的发现，化合物1是具有特征性螺二氢吲哚结构的OPC分化的有效诱导剂。此外，我们发现，Ñ -methylation和DES羰基化合物1（4导致效力损失）。在这里，我们描述了基于螺核的优选构象的基于构象的OPC分化活性假说的研究，进一步的结构-活性关系（SAR）探索导致了6-CF ₃的鉴定衍生物8，比化合物1更有效。