1885-14-9Relevant articles and documents
Rational design and screening study of novel lead compound based on acetohydroxyacid synthase structure
Jin, Jingnan,Qi, Xiaojuan,Yao, Dandan,Mao, Bangqiang,Li, Jianhong,Zhang, Qingye,Chen, Changshui
, p. 316 - 324 (2014)
Acetohydroxyacid synthase (AHAS) is a key target and has extensive application in the process of herbicide discovery. However, the problem of weed resistance is gradually serious with long-term excessive use of commercial AHAS-inhibiting herbicides, and so, it is urgent to develop novel herbicides. In this study, a virtual screening was performed based on the active site of AHAS. Then, the hit-10 compound with the IC50 value of 47.41 mg/L was selected as lead compound based on the biological testing. Subsequently, the optimization design and syntheses of lead compound were carried out according to the analyzing results of mechanism and receptor-/ligand-binding mode. Three novel 5-substituted benzyl-1,3,4-thiadiazol-2-carbamic acid phenyl ester derivatives were designed and synthesized. Bioactive assay results of the three target compounds showed that all of them displayed the higher inhibition than lead compound to AHAS, with the IC50 values in the 23.54-32.05 mg/L range, and the inhibition rates were increased by 30-50%. Finally, we also analyzed the possible inhibitory mechanism of the three target compounds based on the molecular docking between AHAS and target compounds. This study would provide a novel chemical structure for the discovery of novel AHAS herbicides. Lead compound with IC50 value of 47.41 mg/L was screened out based on AHAS target. Optimization and syntheses of lead compound were performed, and the inhibition rates of the synthesized compound increased by 30-50%. The possible inhibitory mechanisms were analyzed by molecular docking.
Synthesis of N-trifluoromethyl amides from carboxylic acids
Flavell, Robert R.,Liu, Jianbo,Parker, Matthew F. L.,Toste, F. Dean,Wang, Sinan,Wilson, David M.
supporting information, p. 2245 - 2255 (2021/08/12)
Found in biomolecules, pharmaceuticals, and agrochemicals, amide-containing molecules are ubiquitous in nature, and their derivatization represents a significant methodological goal in fluorine chemistry. Trifluoromethyl amides have emerged as important functional groups frequently found in pharmaceutical compounds. To date, there is no strategy for synthesizing N-trifluoromethyl amides from abundant organic carboxylic acid derivatives, which are ideal starting materials in amide synthesis. Here, we report the synthesis of N-trifluoromethyl amides from carboxylic acid halides and esters under mild conditions via isothiocyanates in the presence of silver fluoride at room temperature. Through this strategy, isothiocyanates are desulfurized with AgF, and then the formed derivative is acylated to afford N-trifluoromethyl amides, including previously inaccessible structures. This method shows broad scope, provides a platform for rapidly generating N-trifluoromethyl amides by virtue of the diversity and availability of both reaction partners, and should find application in the modification of advanced intermediates.
Versatile Cp*Co(III)(LX) Catalyst System for Selective Intramolecular C-H Amidation Reactions
Chang, Sukbok,Jung, Hoimin,Kim, Dongwook,Lee, Jeonghyo,Lee, Jia,Park, Juhyeon
supporting information, p. 12324 - 12332 (2020/08/06)
Herein, we report the development of a tailored cobalt catalyst system of Cp*Co(III)(LX) toward intramolecular C-H nitrene insertion of azidoformates to afford cyclic carbamates. The cobalt complexes were easy to prepare and bench-stable, thus offering a convenient reaction protocol. The catalytic reactivity was significantly improved by the electronic tuning of the bidentate LX ligands, and the observed regioselectivity was rationalized by the conformational analysis and DFT calculations of the transition states. The superior performance of the newly developed cobalt catalyst system could be broadly applied to both C(sp2)-H and C(sp3)-H carbamation reactions under mild conditions.
Discovery of (3-Benzyl-5-hydroxyphenyl)carbamates as new antitubercular agents with potent in vitro and in vivo efficacy
Cheng, Ya-Juan,Liu, Zhi-Yong,Liang, Hua-Ju,Fang, Cui-Ting,Zhang, Niu-Niu,Zhang, Tian-Yu,Yan, Ming
, (2019/06/07)
A series of 3-amino-5-benzylphenol derivatives were designed and synthesized. Among them, (3-benzyl-5-hydroxyphenyl)carbamates were found to exert good inhibitory activity against M. tuberculosis H37Ra, H37Rv and clinically isolated multidrug-resistant M. tuberculosis strains (MIC = 0.625-6.25 μg/mL). The privileged compounds 3i and 3l showed moderate cytotoxicity against cell line A549. Compound 3l also exhibited potent in vivo inhibitory activity on a mouse infection model via the oral administration. The results demonstrated 3-hydroxyphenylcarbamates as a class of new antitubercular agents with good potential.