19182-81-1Relevant articles and documents
2,4-Dinitroimidazole: Microwave Assisted Synthesis and Use in Synthesis of 2,3-Dihydro-6-nitroimidazo[2,1-b]oxazole Analogues with Antimycobacterial Activity
Bhaumik, Kankan,Akamanchi
, p. 51 - 55 (2004)
2,4-Dinitroimidazole (2,4-DNI), an important starting material for nitroimidazooxazole and nitroimidazooxazine types of antitubercular agents was synthesized by rearrangement of 1,4-dinitroimidazole (1,4-DNI) under microwave irradiation. Various new nitro
High-energy-density materials based on 1-nitramino-2,4-dinitroimidazole
Song, Jinhong,Wang, Kai,Liang, Lixuan,Bian, Chengming,Zhou, Zhiming
, p. 10859 - 10866 (2013)
New energetic salts based on 1-nitramino-2,4-dinitroimidazole were successfully synthesized. The salts were fully characterized by 1H, 13C NMR and IR spectroscopy, differential scanning calorimetry (DSC), and elemental analyses. The salts were found to have good physical and detonation properties. The structure of guanidinium salt (3) was further confirmed by single-crystal X-ray diffraction. The densities of the energetic salts ranged between 1.70 and 1.93 g cm-3 as measured by a gas pycnometer. The detonation pressures and velocities calculated by the EXPLO5 code ranged within 29.3-40.5 GPa and 8370-9209 m s-1, respectively. The Royal Society of Chemistry 2013.
Synthesis, thermal hazard analysis and density functional theory study of nitroimidazoles
Hao, Lina,Jiang, Juncheng,Liu, Xuqin,Ma, Congming,Ma, Peng,Pan, Yong,Xu, Xiaosong,Zhang, Renfa
, (2021/11/16)
To understand the thermal decomposition mechanism and performance of nitroimidazoles, 1,4-dinitroimidazole (1,4-DNI), 2,4-dinitroimidazole (2,4-DNI) and 4,5-dinitroimidazole (4,5-DNI) were synthesized by 4-nitroimidazole firstly and all of them were studied using Differential Scanning Calorimetry (DSC), Accelerating Rate Calorimetry (ARC) and Density Functional Theory (DFT). The experiments show that among the four nitroimidazoles, the decomposition temperature and apparent activation energy of 1,4-DNI are relatively low. Theoretical calculations show that compared with C[sbnd]NO2, N[sbnd]NO2 is easier to break from the imidazole ring, and the detonation performance of 1,4-DNI is the best among the four nitroimidazoles. Dinitroimidazoles all contain two nitro groups, resulting in their sensitivity and energy much greater than 4-NI. Since 1,4-DNI is the only substance containing N[sbnd]NO2, the chemical activity of 1,4-DNI is further improved. In addition, 1,4-DNI has relatively excellent detonation performance, which can be used as the research direction of new energetic materials.
Discovery of WD Repeat-Containing Protein 5 (WDR5)-MYC Inhibitors Using Fragment-Based Methods and Structure-Based Design
Chacón Simon, Selena,Wang, Feng,Thomas, Lance R.,Phan, Jason,Zhao, Bin,Olejniczak, Edward T.,MacDonald, Jonathan D.,Shaw, J. Grace,Schlund, Caden,Payne, William,Creighton, Joy,Stauffer, Shaun R.,Waterson, Alex G.,Tansey, William P.,Fesik, Stephen W.
, p. 4315 - 4333 (2020/05/25)
The frequent deregulation of MYC and its elevated expression via multiple mechanisms drives cells to a tumorigenic state. Indeed, MYC is overexpressed in up to ?50% of human cancers and is considered a highly validated anticancer target. Recently, we discovered that WD repeat-containing protein 5 (WDR5) binds to MYC and is a critical cofactor required for the recruitment of MYC to its target genes and reported the first small molecule inhibitors of the WDR5-MYC interaction using structure-based design. These compounds display high binding affinity, but have poor physicochemical properties and are hence not suitable for in vivo studies. Herein, we conducted an NMR-based fragment screening to identify additional chemical matter and, using a structure-based approach, we merged a fragment hit with the previously reported sulfonamide series. Compounds in this series can disrupt the WDR5-MYC interaction in cells, and as a consequence, we observed a reduction of MYC localization to chromatin.
Structure-Based Design of 6-Chloro-4-aminoquinazoline-2-carboxamide Derivatives as Potent and Selective p21-Activated Kinase 4 (PAK4) Inhibitors
Hao, Chenzhou,Zhao, Fan,Song, Hongyan,Guo, Jing,Li, Xiaodong,Jiang, Xiaolin,Huan, Ran,Song, Shuai,Zhang, Qiaoling,Wang, Ruifeng,Wang, Kai,Pang, Yu,Liu, Tongchao,Lu, Tianqi,Huang, Wanxu,Wang, Jian,Lin, Bin,He, Zhonggui,Li, Haitao,Li, Feng,Zhao, Dongmei,Cheng, Maosheng
, p. 265 - 285 (2018/02/10)
Herein, we report the discovery and characterization of a novel class of PAK4 inhibitors with a quinazoline scaffold. Based on the shape and chemical composition of the ATP-binding pocket of PAKs, we chose a 2,4-diaminoquinazoline series of inhibitors as a starting point. Guided by X-ray crystallography and a structure-based drug design (SBDD) approach, a series of novel 4-aminoquinazoline-2-carboxamide PAK4 inhibitors were designed and synthesized. The inhibitors' selectivity, therapeutic potency, and pharmaceutical properties were optimized. One of the best compounds, 31 (CZh226), showed remarkable PAK4 selectivity (346-fold vs PAK1) and favorable kinase selectivity profile. Moreover, this compound potently inhibited the migration and invasion of A549 tumor cells by regulating the PAK4-directed downstream signaling pathways in vitro. Taken together, these data support the further development of 31 as a lead compound for PAK4-targeted anticancer drug discovery and as a valuable research probe for the further biological investigation of group II PAKs.
