化学
喹唑啉
体外
PI3K/AKT/mTOR通路
活力测定
酶
组合化学
癌症研究
生物化学
药理学
计算生物学
立体化学
生物
信号转导
作者
Aisha A. K. Al-Ashmawy,Khaled M. Elokely,Óscar Cano Pérez,Mario C. Rico,John Gordon,George Mateo,Abdelsattar M. Omar,Magid Abou‐Gharbia,Wayne E. Childers
标识
DOI:10.1021/acsmedchemlett.0c00289
摘要
The dual PI3Kα/ m TOR inhibitors represent a promising molecularly targeted therapy for cancer. Here, we documented the discovery of new 2,4-disubstituted quinazoline analogs as potent dual PI3Kα/sm TOR inhibitors. Our structure based chemistry endeavor yielded six excellent compounds 9e, 9f, 9g, 9k, 9m, and 9o with single/double digit nanomolar IC50 values against both enzymes and acceptable aqueous solubility and stability to oxidative metabolism. One of those analogs, 9m, possessed a sulfonamide substituent, which has not been described for this chemical scaffold before. The short direct synthetic routes, structure-activity relationship, in vitro 2D cell culture viability assays against normal fibroblasts and 3 breast cancer cell lines, and in vitro 3D culture viability assay against MCF7 cells for this series are described.
科研通智能强力驱动
Strongly Powered by AbleSci AI