Yan, Guoyi; Pu, Chunlan; Lan, Suke; Zhong, Xinxin; Zhou, Meng; Hou, Xueyan; Yang, Jie; Shan, Huifang; Zhao, Lifeng; Li, Rui published the artcile< Discovery of 4-phenyl-2H-benzo[b][1,4]oxazin-3(4H)-one derivatives as potent and orally active PI3K/mTOR dual inhibitors>, Quality Control of 112-63-0, the main research area is benzooxazinone preparation SAR PI3K mTOR dual inhibitor antitumor human; Cancer treatment; Dual inhibitor; PI3K/mTOR; Structural optimization.
PI3K/Akt/mTOR signaling pathway plays an important role in cancer cell growth and survival. In this study, a new class of mols. with skeleton of 4-phenyl-2H-benzo[b][1,4]oxazin-3(4H)-one I (X = H, F, Cl, etc.; R1 = 4-HOC6H4, 3-quinoline, 3-(4-fluoro-benzenesulfonamido)phenyl, etc.) II (R = i-Pr, cyclopropyl, Cy; R1 = 4-HOC6H4, 3-quinoline, 3-(4-fluoro-benzenesulfonamido)phenyl, etc.) were designed and synthesized targeting this pathway. Bioassays showed that, among all the mols., I (X = 4-OMe; R1 = 2-methoxy-3-(4-fluoro-benzenesulfonamido)pyrid-5-yl) was a pan-class I PI3K/mTOR inhibitor with an IC50 of 0.63 nM against PI3Kα. In a wide panel of protein kinases assays, no off-target interactions of I (X = 4-OMe; R1 = 2-methoxy-3-(4-fluoro-benzenesulfonamido)pyrid-5-yl) were identified. I (X = 4-OMe; R1 = 2-methoxy-3-(4-fluoro-benzenesulfonamido)pyrid-5-yl) was orally available, and displayed favorable pharmacokinetic parameters in mice (oral bioavailability of 24.1%). In addition, I (X = 4-OMe; R1 = 2-methoxy-3-(4-fluoro-benzenesulfonamido)pyrid-5-yl) demonstrated significant efficiency in Hela/A549 tumor xenograft models (TGI of 87.7% at dose of 50 mg/kg in Hela model) without causing significant weight loss and toxicity during 30 days treatment. Based on the bioassays, compound I (X = 4-OMe; R1 = 2-methoxy-3-(4-fluoro-benzenesulfonamido)pyrid-5-yl) could be used as an anti-cancer drug candidate.
European 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, Quality Control of 112-63-0.
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics