36388-29-1Relevant academic research and scientific papers
Design, synthesis and evaluation of novel 9-arylalkyl-10-methylacridinium derivatives as highly potent FtsZ-targeting antibacterial agents
Song, Di,Zhang, Nan,Zhang, Panpan,Zhang, Na,Chen, Weijin,Zhang, Long,Guo, Ting,Gu, Xiaotong,Ma, Shutao
, (2021/05/10)
With the increasing incidence of antibiotic resistance, new antibacterial agents having novel mechanisms of action hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. Four novel series of substituted 9-arylalkyl-10-methylacridinium derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their antibacterial activities against various Gram-positive and Gram-negative bacteria. The results demonstrated that they exhibited broad-spectrum activities with substantial efficacy against MRSA and VRE, which were superior or comparable to the berberine, sanguinarine, linezolid, ciprofloxacin and vancomycin. In particular, the most promising compound 15f showed rapid bactericidal properties, which avoid the emergence of drug resistance. However, 15f showed no inhibitory effect on Gram-negative bacteria but biofilm formation study gave possible answers. Further target identification and mechanistic studies revealed that 15f functioned as an effective FtsZ inhibitor to alter the dynamics of FtsZ self-polymerization, which resulted in termination of the cell division and caused cell death. Further cytotoxicity and animal studies demonstrated that 15f not only displayed efficacy in a murine model of bacteremia in vivo, but also no significant hemolysis to mammalian cells. Overall, this compound with novel skeleton could serve as an antibacterial lead of FtsZ inhibitor for further evaluation of drug-likeness.
Pd-Catalyzed Approach for Assembling 9-Arylacridines via a Cascade Tandem Reaction of 2-(Arylamino)benzonitrile with Arylboronic Acids in Water
Ye, Xuanzeng,Xu, Beihang,Sun, Jiani,Dai, Ling,Shao, Yinlin,Zhang, Yetong,Chen, Jiuxi
, p. 13004 - 13014 (2020/11/23)
A novel palladium-catalyzed protocol for the synthesis of 9-arylacridines via tandem reaction of 2-(arylamino)benzonitrile with arylboronic acids in water has been developed with good functional group tolerance. The present synthetic route could be readily scaled up to gram quantity without difficulty. This methodology was further extended to the synthesis of a 4′-OH derivative, which showed estrogenic biological activity. Preliminary mechanistic experiments showed that this transformation involves a nucleophilic addition of aryl palladium species to the nitrile to generate an aryl ketone intermediate followed by an intramolecular Friedel-Crafts acylation and dehydration to acridines.
Preparation method of 9-phenyl acridine compound (by machine translation)
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Paragraph 0040; 0041, (2019/11/21)
The preparation method comprises the following 9 - steps: under the action 1 of a palladium catalyst, reacting the halogenated acridine compound of the formula I with 2 the phenylboronic acid or derivative thereof in a solvent under the action of a palladium catalyst 20 - 80 °C 3 9 . The halogen atom in the first X alkyl R group is 1 - 18 at least one halogen atom, and the alkyl group second is an alkyl group, an alkenyl group, an alkynyl group or a halogen atom. By adopting the method disclosed by the invention, the reaction 97% conversion rate is equal to or higher, the finished 99% product content after being subjected to post-treatment is higher than or equal to, and the process can meet the requirements of industrial production. (by machine translation)
Phosphine ligand for indole skeleton as well as preparation method and application of phosphine ligand
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Paragraph 0212; 0215; 0221-0225; 0227, (2017/12/30)
The invention provides a phosphine ligand for a 3-(disubstituted phosphino)-1-alkyl-2-substituted phenyl-indole skeleton as well as a preparation method and application of the phosphine ligand. The structure of the phosphine ligand for the 3-(disubstituted phosphino)-1-alkyl-2-substituted phenyl-indole skeleton is shown as the following formula I: (shown in the description), wherein Z is carbon or nitrogen, R is alkyl, substituted alkyl, olefin, aryl or fluorine, R1 is alkyl, substituted alkyl or aryl, R2 is alkyl, substituted alkyl or fluorine, and R3 is alkyl, substituted alkyl or aryl.
Synthesis of Substituted Acridines through a Palladium-Catalyzed Condensation/Cyclization/Tautomerization Sequence
Chen, Xiangui,Xie, Yanjun,Li, Cheng,Xiao, Fuhong,Deng, Guo-Jun
supporting information, p. 577 - 581 (2017/02/05)
Herein, we report an efficient strategy for the synthesis of 9-aryl-substituted acridines from cyclohexanones and 2-aminobenzophenones in the presence of a palladium catalyst. Molecular oxygen is applied as a green oxidant. Various cyclohexanones acted as the aryl source to construct the nitrogen-containing heterocycles through a condensation/cyclization/tautomerization sequence.
