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 , and with single/double digit nanomolar IC values against both enzymes and acceptable aqueous solubility and stability to oxidative metabolism. One of those analogs, , possessed a sulfonamide substituent, which has not been described for this chemical scaffold before. The short direct synthetic routes, structure-activity relationship, 2D cell culture viability assays against normal fibroblasts and 3 breast cancer cell lines, and 3D culture viability assay against MCF7 cells for this series are described.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667832 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.0c00289 | DOI Listing |
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