A131 (1) possesses a unique cancer cell selective dual mechanism of action where cancer cells are killed but normal cells only undergo growth arrest and are able to regrow after removal of 1. SAR studies of 1 indicate that only the specific structure of 1 elicits the full pharmacological effect. However, application of 1 in mouse models of cancer has been hampered by its low solubility and stability when given orally. In this work we describe the study of various prodrugs based on modification of the indole nitrogen. A range of acyl analogues were prepared as prodrugs which were shown to undergo degradation to the parent drug in plasma. A preferred prodrug fully elicited the pharmacological effects of 1 in cells and led to high aqueous solubility suitable for oral administration. In a mouse model of paclitaxel-resistant colon cancer, compound 10, as a TFA salt, showed 76% tumor growth inhibition when administered at an oral dose of 80 mg/kg twice a day.

A131（1）具有独特的癌细胞选择性双重作用机制，癌细胞被杀死，但正常细胞仅经历生长停滞，并在除去1后能够重新生长。合成孔径雷达研究1表明，只有特定的结构1所引起充分的药理作用。但是，口服给药时1的低溶解度和稳定性已经阻碍了1在癌症小鼠模型中的应用。在这项工作中，我们描述了基于吲哚氮修饰的各种前药的研究。制备了一系列酰基类似物作为前药，显示它们在血浆中会降解为母体药物。一种优选的前药可完全引起下列药物的药理作用：1在细胞中并导致高水溶性，适合口服。在紫杉醇抗性结肠癌的小鼠模型中，化合物10以TFA盐的形式，每天两次口服80 mg / kg，表现出76％的肿瘤生长抑制作用。