114875-62-6Relevant academic research and scientific papers
Synthesis and in vitro antibacterial activity of new aminothiazole-oximepiperidone cephalosporins
Bian, Hongzhu,Chen, Lixia,Dong, Xun,Shen, Zhengwu,Sheng, Sihan,Xu, Wei,Yu, Jingfeng,Zhang, Jinghua
, (2021)
Four new aminothiazole-oximepiperidone cephalosporins (10a-10d) were synthesized, with their in vitro antibacterial activities against hospital isolated Gram-negative bacteria assessed. The results showed that compounds 10a-10d effectively inhibit a varie
C-3 tetrahydrofuran substituted cephalosporin-siderophore conjugate as well as preparation method and application thereof
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, (2020/09/16)
The invention discloses a C-3-tetrahydrofuran substituted cephalosporin-siderophore conjugate as well as a preparation method and application of the C-3-tetrahydrofuran substituted cephalosporin-siderophore conjugate. The invention discloses the C-3 tetra
Discovery of Novel Pyridone-Conjugated Monosulfactams as Potent and Broad-Spectrum Antibiotics for Multidrug-Resistant Gram-Negative Infections
Tan, Liang,Tao, Yunliang,Wang, Ting,Zou, Feng,Zhang, Shuhua,Kou, Qunhuan,Niu, Ao,Chen, Qian,Chu, Wenjing,Chen, Xiaoyan,Wang, Haidong,Yang, Yushe
, p. 2669 - 2684 (2017/04/21)
Conjugating a siderophore to an antibiotic is a promising strategy to overcome the permeability-mediated resistance of Gram-negative pathogens. On the basis of the structure of BAL30072, novel pyridone-conjugated monosulfactams incorporating diverse substituents into the methylene linker between the 1,3-dihydroxypyridin-4(1H)-one and the aminothiazole oxime were designed and synthesized. Structure-activity relationship studies revealed that a variety of substituents were tolerated, with isopropyl (compound 12c) and methylthiomethyl (compound 16a) showing the best efficacy against multidrug-resistant (MDR) Gram-negative pathogens. In addition, compound 12c exhibits a good free fraction rate in an in vitro human plasma protein binding test, along with a low clearance and favorable plasma exposure in vivo. In a murine systemic infection model with MDR Klebsiella pneumoniae, compound 12c shows an ED50 of 10.20 mg/kg. Taken together, the results indicate that compound 12c is a promising drug candidate for the treatment of serious infections caused by MDR Gram-negative pathogens.
Design, synthesis and biological evaluation of LpxC inhibitors with novel hydrophilic terminus
Ding, Shi,Wang, Wen-Ke,Cao, Qiao,Chu, Wen-Jing,Lan, Le-Fu,Hu, Wen-Hao,Yang, Yu-She
, p. 763 - 767 (2015/08/03)
Abstract In order to develop novel LpxC inhibitors with good activities and metabolic stability, two series of compounds with hydrophilic terminus have been synthesized and their in vitro antibacterial activities against Escherichial coli and Pseudomonas aeruginosa were evaluated. Especially, compounds 22b and c exhibited comparable antibacterial activities to CHIR-090 and better metabolic stability than CHIR-090 and LPC-011 in liver microsomes (rat and mouse), which indicated the terminal methylsulfone may be a preferred structure in the design of LpxC inhibitors and worthy of further investigations.
Pyridone-conjugated monobactam antibiotics with gram-negative activity
Brown, Matthew F.,Mitton-Fry, Mark J.,Arcari, Joel T.,Barham, Rose,Casavant, Jeffrey,Gerstenberger, Brian S.,Han, Seungil,Hardink, Joel R.,Harris, Thomas M.,Hoang, Thuy,Huband, Michael D.,Lall, Manjinder S.,Lemmon, M. Megan,Li, Chao,Lin, Jian,McCurdy, Sandra P.,McElroy, Eric,McPherson, Craig,Marr, Eric S.,Mueller, John P.,Mullins, Lisa,Nikitenko, Antonia A.,Noe, Mark C.,Penzien, Joseph,Plummer, Mark S.,Schuff, Brandon P.,Shanmugasundaram, Veerabahu,Starr, Jeremy T.,Sun, Jianmin,Tomaras, Andrew,Young, Jennifer A.,Zaniewski, Richard P.
, p. 5541 - 5552 (2013/07/26)
Herein we describe the structure-aided design and synthesis of a series of pyridone-conjugated monobactam analogues with in vitro antibacterial activity against clinically relevant Gram-negative species including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Rat pharmacokinetic studies with compound 17 demonstrate low clearance and low plasma protein binding. In addition, evidence is provided for a number of analogues suggesting that the siderophore receptors PiuA and PirA play a role in drug uptake in P. aeruginosa strain PAO1.
MONOBACTAMS
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, (2012/06/16)
The present invention is directed to a new class of monobactam derivatives and their use for treating bacterial infections.
Cephalosporin compounds, and antibacterial agents
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, (2008/06/13)
A cephalosporin compound having the formula: STR1 wherein R1 is a hydrogen atom, a halogen atom, a methoxy group, a substituted or unsubstituted vinyl group, or --CH2 --A wherein A is a hydrogen atom, an azido group, an acyloxy group
