Lin, Songwen; Wang, Chunyang; Ji, Ming; Wu, Deyu; Lv, Yuanhao; Zhang, Kehui; Dong, Yi; Jin, Jing; Chen, Jiajing; Zhang, Jingbo; Sheng, Li; Li, Yan; Chen, Xiaoguang; Xu, Heng published the artcile< Discovery and Optimization of 2-Amino-4-methylquinazoline Derivatives as Highly Potent Phosphatidylinositol 3-Kinase Inhibitors for Cancer Treatment>, Synthetic Route of 112-63-0, the main research area is amino methyl quinazoline derivative preparation PI3K inhibitor cancer.
Increased phosphatidylinositol 3-kinase (PI3K) signaling is among the most common alterations in cancer, spurring intensive efforts to develop new cancer therapeutics that target this pathway. In this work, we discovered a series of novel 2-amino-4-methylquinazoline derivatives through a hybridization and subsequent scaffold hopping approach that were highly potent class I PI3K inhibitors. Lead optimization resulted in several promising compounds (e.g., 19, 20, 37, and 43) with nanomolar PI3K potencies, prominent antiproliferative activities, favorable PK profiles, and robust in vivo antitumor efficacies. More interestingly, compared with 19 and 20, 37 and 43 demonstrated improved brain penetration and in vivo efficacy in an orthotopic glioblastoma xenograft model. Furthermore, preliminary safety assessments including hERG channel inhibition, AMES, CYP450 inhibition, and single-dose toxicity were performed to characterize their toxicol. properties.
Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Synthetic Route of 112-63-0.
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics