A series of IGF-1R inhibitors is disclosed, wherein the (m-chlorophenyl)ethanol side chain of BMS-536924 (1) is replaced with a series of 2-(1H-imidazol-4-yl)ethanamine and 2-(1H-pyrazol-1-yl)ethanamine side chains. Some analogs show improved IGF-1R potency and oral exposure. Analogs from both series, 16a and 17f, show in vivo activity comparable to 1 in our constitutively activated IGF-1R Sal tumor model. This may be the due to the improved protein binding in human and mouse serum for imidazole 16a and the excellent oral exposure of pyrazole 17f.

中文翻译：

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IGF-1R抑制剂BMS-536924的2-（1H-咪唑-4-基）乙胺和2-（1H-吡唑-1-基）乙胺侧链变体。

公开了一系列IGF-1R抑制剂，其中BMS-536924（1）的（间氯苯基）乙醇侧链被一系列2-（1H-咪唑-4-基）乙胺和2-（1H）取代-吡唑-1-基）乙胺侧链。一些类似物显示出改善的IGF-1R效力和口服暴露。在我们的组成型激活的IGF-1R Sal肿瘤模型中，两个系列的类似物16a和17f在体内的活性均与1相当。这可能是由于咪唑16a在人和小鼠血清中蛋白质结合的改善以及吡唑17f的出色口服暴露所致。