5932-27-4Relevant articles and documents
Vinyldiazo Compounds as 3-Carbon Radical Acceptors: Synthesis of 4-Fluoroacridines via Visible-Light-Promoted Cascade Radical Cyclization
Li, Weiyu,Zhou, Lei
, p. 4279 - 4283 (2021)
Vinyldiazo reagents were developed as the radical acceptors in a visible-light-promoted sequential radical cyclization reaction, providing a mechanistically distinct pathway to achieve (3 + 3) cyclization. Using N-aryl chlorodifluoromethyl alkynyl ketoimines as the radical precursors, the reaction allows the introduction of a fluorine atom to the acridine skeleton during the construction of both the pyridine and benzene motifs from acyclic building blocks. The resulting 4-fluoroacridines exhibited pronounced fluorescent properties in the solid state.
1-vinyl-3- and 1-vinyl-5-pyrazolecarboxylic acids. synthesis and anti-burn activity of their chitosan salts
Rstakyan,Akopyan,Saakyan,Attaryan,Asratyan
, p. 1945 - 1949 (2014)
The synthesis of 1-vinyl-3- and 1-vinyl-5-pyrazolcarboxylic acids is developed and the anti burn activity of the chitosan salts of 1-vinyl-3(5)-carboxylic acids is studied.
Design, synthesis and biological evaluation of ring-fused pyrazoloamino pyridine/pyrimidine derivatives as potential FAK inhibitors
Xie, Hongming,Lin, Xinglong,Zhang, Yingjun,Tan, Fuxing,Chi, Bo,Peng, Zhihong,Dong, Wanrong,An, Delie
supporting information, (2020/10/06)
We report herein the synthesis of novel ring-fused pyrazoloamino pyridine/pyrimidine derivatives as potential FAK inhibitors and the evaluation of pharmaceutical activity against five cancer cell lines (MDA-MB-231, BXPC-3, NCI-H1975, DU145 and 786O). Generally, the majority of compounds displayed strong anti-FAK enzymatic potencies (IC50 1 nM) and could effectively inhibit several class of cancer cell lines within the concentration of 3 μM in comparison with GSK2256098 as a reference. Among them, compound 4o is considered to be the most effective due to high sensitivity in antiproliferation. In culture, 4o could not only inhibit FAK Y397 phosphorylation in MDA-MB-231 cell line, but also trigger apoptosis in a dose-dependent manner. Furthermore, computational docking analysis also suggested that 4o and TAE-226 displayed the similar interaction with FAK kinase domain.
Structure Kinetics Relationships and Molecular Dynamics Show Crucial Role for Heterocycle Leaving Group in Irreversible Diacylglycerol Lipase Inhibitors
Janssen, Antonius P.A.,Van Hengst, Jacob M.A.,Béquignon, Olivier J.M.,Deng, Hui,Van Westen, Gerard J.P.,Van Der Stelt, Mario
, p. 7910 - 7922 (2019/10/11)
Drug discovery programs of covalent irreversible, mechanism-based enzyme inhibitors often focus on optimization of potency as determined by IC50-values in biochemical assays. These assays do not allow the characterization of the binding activity (Ki) and reactivity (kinact) as individual kinetic parameters of the covalent inhibitors. Here, we report the development of a kinetic substrate assay to study the influence of the acidity (pKa) of heterocyclic leaving group of triazole urea derivatives as diacylglycerol lipase (DAGL)-α inhibitors. Surprisingly, we found that the reactivity of the inhibitors did not correlate with the pKa of the leaving group, whereas the position of the nitrogen atoms in the heterocyclic core determined to a large extent the binding activity of the inhibitor. This finding was confirmed and clarified by molecular dynamics simulations on the covalently bound Michaelis-Menten complex. A deeper understanding of the binding properties of covalent serine hydrolase inhibitors is expected to aid in the discovery and development of more selective covalent inhibitors.
