The thiazolidinedione, compound 1, has previously shown pan-inhibition of the phosphoinositide 3-kinase (PI3K) class I isoforms. We hypothesized the derivatization of the thiazolidinedione core of compound 1 could introduce isoform selectivity. We report the synthesis, characterization, and inhibitory activity of a novel series of 4-iminothiazolidin-2-ones for inhibition of the class I PI3K isoforms. Their synthesis was successfully achieved by multiple pathways described in this paper. Initial in vitro data of 28 analogues demonstrated poor inhibition of all class I PI3K isoforms. However, we identified an alternate target, the phosphodiesterases, and present preliminary screening results showing improved inhibitory activity.

噻唑烷二酮化合物1先前已显示出对磷酸肌醇 3-激酶 (PI3K) I 类同工型的泛抑制。我们假设化合物1的噻唑烷二酮核心的衍生化可以引入同工型选择性。我们报告了一系列新型 4-iminothiazolidin-2-ones 的合成、表征和抑制活性，用于抑制 I 类 PI3K 亚型。它们的合成是通过本文中描述的多种途径成功实现的。28 种类似物的初始体外数据表明对所有 I 类 PI3K 同工型的抑制作用较差。然而，我们确定了一个替代目标，即磷酸二酯酶，并提供了初步筛选结果，表明抑制活性有所提高。