6622-55-5Relevant articles and documents
Melatonin derivatives combat with inflammation-related cancer by targeting the Main Culprit STAT3
Ma, Shumeng,Zhu, Longqing,Fan, Xiaohong,Luo, Tian,Liu, Dan,Liang, Ziyi,Hu, Xiaoling,Shi, Tao,Tan, Wen,Wang, Zhen
, (2020/12/02)
The combination between two well-studied bioactive compounds melatonin and salicylic acid with proper modifications unexpectedly creates a sharp pair of “scissors” cutting off the vicious connection between inflammation and cancer by targeting a key contributor Signal Transducers and Activators of Transcription 3 (STAT3) in the two pathological processes. A representative compound P-3 with IC50 values on each tested cell line ranging from 7.37 to 18.62 μM among the designed melatonin derivatives is equipped with the ability of curbing inflammation-promoting cancer by down-regulating the expression, activation and nuclear translocation of STAT3, breaking the feedforward loop of STAT3 activation by decreasing the expression of pro-tumorigenic cytokines, and inducing cell apoptosis through ROS triggered Cyto-c/Caspase-3 pathway. This study suggests that the melatonin derivative P-3 is likely to become a promising chemical structure for developing the novel anti-cancer agents taking effect through hindering the mutual-promoting processes between inflammation and cancer.
Sulfate Radical Anion (SO4?-) Mediated C(sp3)-H Nitrogenation/Oxygenation in N-Aryl Benzylic Amines Expanded the Scope for the Synthesis of Benzamidine/Oxazine Heterocycles
Laha, Joydev K.,Tummalapalli, K. S. Satyanarayana,Nair, Akshay,Patel, Nidhi
, p. 11351 - 11359 (2015/12/01)
A transition-metal-free, K2S2O8-mediated intramolecular oxidative nitrogenation/oxygenation of C(sp3)-H in N-aryl benzylic amines followed by oxidation at the benzylic center has been developed for the synthesis of benzamidine/benzoxazine heterocycles, providing an expedient access to quinazolin-4(3H)-ones, N-aryl-2-arylbenzimidazoles, and 4H-3,1-benzoxazin-4-ones. A considerable amount of work dealing with the mechanistic study to understand the crucial intramolecular cyclization step largely favors an iminium ion as the key intermediate.
Palladium-catalyzed benzylic C-H benzylation via bis-benzylpalladium(II) complexes in water: An effective pathway for the direct construction of N-(1,2-diphenylethyl)anilines
Hikawa, Hidemasa,Izumi, Kyoko,Ino, Yukari,Kikkawa, Shoko,Yokoyama, Yuusaku,Azumaya, Isao
, p. 1037 - 1048 (2015/03/30)
A strategy for the N-benzylation/benzylic C-H benzylation cascade of anilines by the π-benzylpalladium system using a water-soluble palladium(0)/sodium diphenylphosphinobenzene-3-sulfonate (TPPMS) catalyst and benzyl alcohol in water has been developed. This tandem process is devised as a novel and efficient synthetic route for N-(1,2-diphenylethyl)anilines. Benzylic C-H activation of a mono-N-benzylated intermediate with a π-benzylpalladium(II) complex affords a bis-π-benzylated palladium(II) intermediate. The nucleophilic η1-σ-benzyl anion ligand attacks the electrophilic η3-π-benzyl ligand to give a dibenzylated product. The intermolecular competition between mono-N-benzylaniline and its monodeuterated form (monodeuterated at the benzylic group) with benzyl alcohol gave a KIE=4.6, suggesting that C-H bond cleavage was involved in the rate-determining step. Hammett studies on the rate constants of benzylation by various substituted anthranilic acids and mono-N-benzylanilines show a good correlation between the log(kX/kH) and the σ values of the respective substituents. From the slope, negative ρ values are obtained, suggesting that there is a build-up of positive charge in the transition state. The reaction of anilines with electron-donating and electron-withdrawing groups affords the corresponding N-(1,2-diphenylethyl)anilines in moderate to good yields (54-86%). Interestingly, the reaction of anthranilic acids proceeded smoothly to give only the corresponding dibenzylated products in good to excellent yields (70-87%). The carboxyl group of the anthranilic acids acts as a directing group in the benzylic C-H activation process.
