1604802-47-2Relevant academic research and scientific papers
Design, synthesis, and biological evaluation of thieno[3,2-d]pyrimidine derivatives as potential simplified phosphatidylinositol 3-kinase alpha inhibitors
Yang, Xiuyan,Deng, Meng,Zhang, Xi,Wang, Yi,Song, Kun,Cong, Ruan,Meng, Linghua,Zhang, Jian
, p. 2013 - 2022 (2019)
A series of thieno[3,2-d]pyrimidine derivatives as phosphatidylinositol 3-kinase (PI3K) inhibitors was designed using the combination strategy. The synthesis and biological evaluation of the derivatives demonstrated their potent inhibition of PI3K, culminating in the discovery of 7 and 21. Determination of a co-crystal structure of 7 complexed with PI3Kα provided the structural basis for the high enzymatic activity. Furthermore, cellular investigation of compounds 7 and 21 revealed that they efficiently suppressed cancer cell lines proliferation through inhibition of intracellular PI3K/AKT/mammalian target of rapamycin pathway. The results provided potent simplified inhibitors of PI3K with a promising overall profile and a chemical series for further optimization to progress into vivo experiments.
