32578-25-9Relevant academic research and scientific papers
Design, Synthesis, and Structure-Activity Relationships of Indoline-Based Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-Derived 2)-Like 2 (Keap1-Nrf2) Protein-Protein Interaction Inhibitors
Zhou, Hai-Shan,Hu, Lv-Bin,Zhang, Han,Shan, Wen-Xin,Wang, Yan,Li, Xue,Liu, Tian,Zhao, Jing,You, Qi-Dong,Jiang, Zheng-Yu
supporting information, p. 11149 - 11168 (2020/11/09)
The Keap1 (Kelch-like ECH-associated protein 1)-Nrf2 (nuclear factor erythroid 2-related factor 2)-ARE (antioxidant response element) pathway is the major defending mechanism against oxidative stresses, and directly disrupting the Keap1-Nrf2 protein-protein interaction (PPI) has been an attractive strategy to target oxidative stress-related diseases, including cardiovascular diseases. Here, we describe the design, synthesis, and structure-activity relationships (SARs) of indoline-based compounds as potent Keap1-Nrf2 PPI inhibitors. Comprehensive SAR analysis and thermodynamics-guided optimization identified 19a as the most potent inhibitor in this series, with an IC50 of 22 nM in a competitive fluorescence polarization assay. Further evaluation indicated the proper drug-like properties of 19a. Compound 19a dose-dependently upregulated genes and protein level of Nrf2 as well as its downstream markers and showed protective effects against lipopolysaccharide-induced injury in both H9c2 cardiac cells and mouse models. Collectively, we reported here a novel indoline-based Keap1-Nrf2 PPI inhibitor as a potential cardioprotective agent.
First Study of the Thermal and Storage Stability of Arenediazonium Triflates Comparing to 4-Nitrobenzenediazonium Tosylate and Tetrafluoroborate by Calorimetric Methods
Bondarev, Alexander A.,Naumov, Evgeny V.,Kassanova, Assiya Zh.,Krasnokutskaya, Elena A.,Stankevich, Ksenia S.,Filimonov, Victor D.
, p. 2405 - 2415 (2019/10/11)
Herein, for the first time, using isothermal flow calorimetry and differential scanning calorimetry (DSC)/thermal gravimetric analysis (TGA), we have determined the thermal decomposition energies for the number of solid arenediazonium triflates comparing to 4-nitrobenzene tosylate and 4-nitrobenzentetrafluoroborate. The kinetics of thermal decomposition, activation energies, and half-lives of the studied diazonium salts (DSs) were found. Using gas chromatography-mass spectrometry (MS) and liquid chromatography-MS, we have elucidated the products formed during thermolysis of the investigated DSs. By density functional theory quantum chemical calculations at the B3LYP/aug-cc-pVDZ level of theory, we simulated the thermodynamics of decomposition reactions proceeding via substitution of the diazonium group by corresponding nucleophiles. The method applied predicted the decomposition energies of all the studied compounds fairly precise, except for 2-nitrobenzene diazonium triflate. It has been found that 4-nitrobenzene diazonium triflate has increased storage stability under normal conditions comparing to the corresponding tosylate and tetrafluoroborate. The experimental and theoretical results demonstrated that comparing to DSC/TGA, isothermal flow calorimetry more adequately reflects the energetics of the thermal decomposition of DSs and their storage stability under normal conditions.
Pd-Catalyzed Difluoromethylthiolation of Aryl Chlorides, Bromides and Triflates
Wu, Jiang,Lu, Changhui,Lu, Long,Shen, Qilong
supporting information, p. 1031 - 1034 (2018/09/25)
A highly efficient Pd-catalyzed difluoromethylthiolation of aryl chlorides, bromides and triflates is described. A variety of aryl halides with common functional groups were difluoromethylthiolated in moderate to excellent yields. Furthermore, several nat
Cesium carbonate mediated aryl triflate esters' deprotection
Green, Alice E.,Agouridas, Vangelis,Deniau, Eric
supporting information, p. 7078 - 7079 (2013/12/04)
A variety of diversely substituted aryl triflate esters were efficiently deprotected to the parent phenols by exposure to cesium carbonate in toluene. This procedure proved highly compatible with existing functional groups.
The conversion of phenols to the corresponding aryl halides under mild conditions
Thompson, Alicia L. S.,Kabalka, George W.,Akula, Murthy R.,Huffman, John W.
, p. 547 - 550 (2007/10/03)
Mild, novel procedures have been developed for the syntheses of aryl halides from the corresponding phenols in modest to good yields via boronate ester intermediates.
A Facile Preparation of Aryl Triflates. Decomposition of Arenediazonium Tetrafluoroborate Salts in Trifluoromethanesulfonic Acid
Yoneda, Norihiko,Fukuhara, Tsuyoshi,Mizokami, Takao,Suzuki, Akira
, p. 459 - 460 (2007/10/02)
The thermal or photochemical decomposition of arenediazonium tetrafluoroborate salts n trifluoromethanesulfonic acid, with or without organic bases such as pyridine, provides aryl triflates in high yields.
