Oncology Chemistry, Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492, USA.
Bioorg Med Chem Lett. 2010 Mar 1;20(5):1744-8. doi: 10.1016/j.bmcl.2010.01.087. Epub 2010 Jan 21.
The SAR of PXR transactivation by 3-(benzimidazol-2-yl)-pyridine-2-one based ATP competitive inhibitors of Insulin-like Growth Factor 1 Receptor kinase (IGF-1R) is discussed. Compounds without PXR transactivation, with in vivo antitumor activity, reduced protein binding and improved oral exposure are presented.
讨论了基于胰岛素样生长因子 1 受体激酶（IGF-1R）的 ATP 竞争抑制剂的 3-（苯并咪唑-2-基）-吡啶-2-酮对 PXR 反式激活作用。本文介绍了一些没有 PXR 反式激活作用、具有体内抗肿瘤活性、降低蛋白结合和改善口服暴露的化合物。
