Wang, Ruifeng; Yu, Sijia; Zhao, Xiangxin; Chen, Yixuan; Yang, Bowen; Wu, Tianxiao; Hao, Chenzhou; Zhao, Dongmei; Cheng, Maosheng published the artcile< Design, synthesis, biological evaluation and molecular docking study of novel thieno[3,2-d]pyrimidine derivatives as potent FAK inhibitors>, Product Details of C19H34O2, the main research area is thienopyrimidine preparation FAK inhibition SAR antitumor docking cytotoxicity apoptosis; Apoptosis; FAK inhibitor; Migration; Structure-activity relationship; Thieno[3,2-d]pyrimidine.
A series of 2,7-disubstituted thieno[3,2-d]pyrimidine derivatives I [R1 = 2-methoxy, 3-acetyl, 3-methylsulfonyl, etc.], II [R2 = methylcarbamoyl, piperidine-3-carbonylamino, diethoxyphosphorylmethyl, etc.], III [R3 = H, Me, ethoxy, etc.; R4 = H, fluoro, methyl; R5 = H, fluoro] and IV [R6 = pyrrolidin-3-yl, tetrahydro-2H-pyran-4-yl, piperidin-3-ylmethyl, etc.] were synthesized and evaluated as novel focal adhesion kinase (FAK) inhibitors. The novel 2,7-disubstituted thieno[3,2-d]pyrimidine scaffold was designed as a new kinase inhibitor platform that mimics the bioactive conformation of the well-known diaminopyrimidine motif. Most of the compounds potently suppressed the enzymic activities of FAK and potently inhibited the proliferation of U-87MG, A-549 and MDA-MB-231 cancer cell lines. Among these derivatives, the optimized compound III [R3 = R5 = H, R4 = fluoro] potently inhibited the enzyme (IC50 = 28.2 nM) and displayed stronger potency than TAE-226 in U-87MG, A-549 and MDA-MB-231 cells, with IC50 values of 0.16, 0.27, and 0.19μM, resp. Compound III [R3 = R5 = H, R4 = fluoro] also exhibited relatively less cytotoxicity (IC50 = 3.32μM) toward a normal human cell line, HK2. According to the flow cytometry results, compound III [R3 = R5 = H, R4 = fluoro] induced the apoptosis of MDA-MB-231 cells in a dose-dependent manner and effectively arrested MDA-MB-231 cells in G0/G1 phase. Further investigations revealed that compound III [R3 = R5 = H, R4 = fluoro] potently suppressed the migration of MDA-MB-231 cells. Collectively, these data support the further development of compound III [R3 = R5 = H, R4 = fluoro] as a lead compound for FAK-targeted anticancer drug discovery.
European Journal of Medicinal Chemistry published new progress about Anilines Role: ADV (Adverse Effect, Including Toxicity), PAC (Pharmacological Activity), PRP (Properties), RCT (Reactant), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), RACT (Reactant or Reagent), PREP (Preparation), USES (Uses). 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Product Details of C19H34O2.
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