18226-25-0Relevant academic research and scientific papers
Structure-Based Optimization of 3-Phenyl-N-(2-(3-phenylureido)ethyl)thiophene-2-sulfonamide Derivatives as Selective Mcl-1 Inhibitors
Li, Yan,Fan, Wenjie,Gong, Qineng,Tian, Jie,Zhou, Mi,Li, Qing,Uwituze, Laura B.,Zhang, Zhichao,Hong, Ran,Wang, Renxiao
, p. 10260 - 10285 (2021/07/26)
Selective Mcl-1 inhibitors may overcome the drug resistance caused by current anti-apoptotic Bcl-2 protein inhibitors in tumors with Mcl-1 overexpression. Based on previously discovered compounds with a 3-phenylthiophene-2-sulfonamide core moiety, in this work, we have obtained new compounds with improved binding affinity and/or selectivity under the guidance of structure-based design. The most potent compounds achieved sub-micromolar binding affinities to Mcl-1 (Ki～ 0.4 μM) and good cytotoxicity (IC5015N-heteronuclear single-quantum coherence NMR spectra suggested that these compounds bound to the BH3-binding groove on Mcl-1. Several cellular assays revealed that FWJ-D4 as well as its precursor FWJ-D5 effectively induced caspase-dependent apoptosis, and their target engagement at Mcl-1 was confirmed by co-immunoprecipitation experiments. Treatment with FWJ-D5 at 50 mg/kg every 2 days on an RS4;11 xenograft mouse model for 22 days led to 75% reduction in tumor volume without body weight loss.
Additivity of substituent effects in aromatic stacking interactions
Hwang, Jungwun,Li, Ping,Carroll, William R.,Smith, Mark D.,Pellechia, Perry J.,Shimizu, Ken D.
supporting information, p. 14060 - 14067 (2015/01/08)
The goal of this study was to experimentally test the additivity of the electrostatic substituent effects (SEs) for the aromatic stacking interaction. The additivity of the SEs was assessed using a small molecule model system that could adopt an offset face-to-face aromatic stacking geometry. The intramolecular interactions of these molecular torsional balances were quantitatively measured via the changes in a folded/unfolded conformational equilibrium. Five different types of substituents were examined (CH3, OCH3, Cl, CN, and NO2) that ranged from electron-donating to electron-withdrawing. The strength of the intramolecular stacking interactions was measured for 21 substituted aromatic stacking balances and 21 control balances in chloroform solution. The observed stability trends were consistent with additive SEs. Specifically, additive SE models could predict SEs with an accuracy from ±0.01 to ±0.02 kcal/mol. The additive SEs were consistent with Wheeler and Houk's direct SE model. However, the indirect or polarization SE model cannot be ruled out as it shows similar levels of additivity for two to three substituent systems, which were the number of substituents in our model system. SE additivity also has practical utility as the SEs can be accurately predicted. This should aid in the rational design and optimization of systems that utilize aromatic stacking interactions.
Copper-catalyzed direct synthesis of di- and triphenylamines: A dramatic accelerating effect of 2-aminophenols
Li, Yaming,Wang, Huifeng,Jiang, Linlin,Sun, Fangfang,Fu, Xinmei,Duan, Chunying
experimental part, p. 6967 - 6973 (2011/02/25)
Utilizing the dramatic accelerating effect of 2-aminophenols, we developed a copper-catalyzed system for the selective synthesis of di- and triphenylamines. In addition, N- and O-arylation could be achieved in coupling reactions between 2-aminophenol and nitroaryl halides. A copper-catalyzed system for the selective synthesis of di- and triphenylamines has been developed. This new protocol provides a direct and efficient way to synthesize o-hydroxy-substituted di- and triphenylamines. Copyright
