6406-73-1Relevant articles and documents
Continuous flow synthesis of amines from the cascade reactions of nitriles and carbonyl-containing compounds promoted by Pt-modified titania catalysts
Altu?, Cevher,Mu?oz-Batista, Mario J.,Rodríguez-Padrón, Daily,Balu, Alina M.,Romero, Antonio A.,Luque, Rafael
, p. 300 - 306 (2019/01/28)
The effective design of an active and stable catalytic system was performed by a simple modification of a commercial titania with a low platinum loading. The prepared material was fully characterized by XRD, XPS, N2 adsorption-desorption measurements, ICP-MS, TEM and SEM analyses. Such techniques corroborated the successful incorporation of Pt onto the titania surface, without affecting its original structure, morphology and chemical nature. The obtained TiO2-Pt catalyst was effectively applied in several continuous flow reactions between nitriles and carbonyl containing compounds for amine preparation. Remarkably, conversion of levulinic acid, a biomass derived molecule, was achieved with outstanding conversion (87%) and selectivity (80%) to 1-ethyl-5-methylpyrrolidin-2-one. The catalytic system demonstrated a high stability through 120 min of reaction. Moreover, the effect of the nitrile was investigated by performing the reaction with benzonitrile and ethylcyanoacetate. The TiO2-Pt catalyst was also tested in the conversion of benzaldehyde, displaying remarkable results. The influence of substitution in the aromatic ring was investigated using p-nitro-benzaldehyde and p-chloro-benzaldehyde.
Semicarbazone derivatives bearing phenyl moiety: Synthesis, anticancer activity, cell cycle, apoptosis-inducing and metabolic stability study
Ma, Junjie,Ni, Xin,Gao, Yali,Huang, Kun,Wang, Yu,Liu, Jiaan,Gong, Guowei
, p. 351 - 360 (2019/05/07)
A series of semicarbazone derivatives bearing phenyl moiety were synthesized and evaluated for the vitro anticancer activities in four human cancer cell lines (human colon cancer (HT29), human neuroblastoma (SK-N-SH), human breast cancer (MDA-MB-231), and human gastric cancer (MKN45)). Biological evaluation led to the identification of 11q and 11s, which showed excellent anticancer activities against tested cancer cell lines with IC50 values ranging from 0.32 to 1.57μM, respectively, while exhibiting weak cytotoxicity on the normal cells (human umbilical vein endothelial cell (HUVEC)). Flow cytometric assay for cell cycle and apoptosis revealed that 11q and 11s caused an arrest in the Sub-G1 cell cycle and inhibited proliferation of cancer cells by inducing apoptosis in a dose-dependent manner. Further enzymatic assay suggested that 11q and 11s could significantly activated procaspase-3 to caspase-3. Metabolic stability study indicated that 11q and 11s showed moderate stability in vitro in human and rat liver microsomes. In view of promising pharmacological activities of 11q and 11s, which had emerged as the valuable lead for further development in the treatment for cancer.
Discovery of 4-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia
Wang, Yue,Zhi, Yanle,Jin, Qiaomei,Lu, Shuai,Lin, Guowu,Yuan, Haoliang,Yang, Taotao,Wang, Zhanwei,Yao, Chao,Ling, Jun,Guo, Hao,Li, Tonghui,Jin, Jianlin,Li, Baoquan,Zhang, Li,Chen, Yadong,Lu, Tao
, p. 1499 - 1518 (2018/03/05)
A series of 1-H-pyrazole-3-carboxamide derivatives have been designed and synthesized that exhibit excellent FLT3 and CDK inhibition and antiproliferative activities. A structure-activity-relationship study illustrates that the incorporation of a pyrimidine-fused heterocycle at position 4 of the pyrazole is critical for FLT3 and CDK inhibition. Compound 50 (FN-1501), which possesses potent inhibitory activities against FLT3, CDK2, CDK4, and CDK6 with IC50 values in the nanomolar range, shows antiproliferative activities against MV4-11 cells (IC50: 0.008 μM), which correlates with the suppression of retinoblastoma phosphorylation, FLT3, ERK, AKT, and STAT5 and the onset of apoptosis. Acute-toxicity studies in mice show that compound 50 (LD50: 186 mg/kg) is safer than AT7519 (32 mg/kg). In MV4-11 xenografts in a nude-mouse model, compound 50 can induce tumor regression at the dose of 15 mg/kg, which is more efficient than cytarabine (50 mg/kg). Taken together, these results demonstrate the potential of this unique compound for further development into a drug applied in acute-myeloid-leukemia (AML) therapeutics.
