504437-66-5Relevant articles and documents
OXAZOLIDINONE COMPOUNDS, LIPOSOME COMPOSITIONS COMPRISING OXAZOLIDINONE COMPOUNDS AND METHOD OF USE THEREOF
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, (2022/01/04)
Compositions and methods for the treatment of tuberculosis, as well as other mycobacterial and gram positive bacterial infections are disclosed. These compositions contain a highly potent and selective oxazolidinone encapsulated with high efficiency to maximize dosing potential of low toxicity drugs, and are stable in the presence of plasma. The compositions are long circulating and retain their encapsulated drug while in the circulation following intravenous dosing to allow for efficient accumulation at the site of the bacterial or mycobacterial infection. The high doses that can be achieved when combined with the long circulating properties and highly stable retention of the drug allow for a reduced frequency of administration when compared to daily or twice daily administrations of other drugs typically utilized to treat these infections.
Design, synthesis and antibacterial evaluation of novel oxazolidinone derivatives nitrogen-containing fused heterocyclic moiety
Jiang, Jia,Hou, Yunlei,Duan, Meibo,Wang, Baihang,Wu, Yachuang,Ding, Xiudong,Zhao, Yanfang
, (2020/12/17)
A series of novel oxazolidinone derivatives with nitrogen-containing fused heterocyclic moiety were designed and synthesized in this article. Their antibacterial activities were measured against S. aureus, MRSA and MSSA by MIC assay. Most of them exhibite
Optimization of biaryloxazolidinone as promising antibacterial agents against antibiotic-susceptible and antibiotic-resistant gram-positive bacteria
Wu, Yachuang,Ding, Xiudong,Yang, Yifeng,Li, Yingxiu,Qi, Yinliang,Hu, Feng,Qin, Mingze,Liu, Yajing,Sun, Lu,Zhao, Yanfang
, (2019/10/23)
We previously discovered a series of novel biaryloxazolidinone analogues bearing a hydrazone moiety with potent antibacterial activity. However, the most potent compound OB-104 exhibited undesirable chemical and metabolic instability. Herein, novel biaryloxazolidinone analogues were designed and synthesized to improve the chemical and metabolic stability. Compounds 6a-1, 6a-3, 14a-1, 14a-3 and 14a-7 showed significant antibacterial activity against the tested Gram-positive bacteria as compared to radezolid and linezolid. Further studies indicated that most of them exhibited improved water solubility and chemical stability. Compound 14a-7 had MIC values of 0.125–0.25 μg/mL against all tested Gram-positive bacteria, and showed excellent antibacterial activity against clinical isolates of antibiotic-susceptible and antibiotic-resistant bacteria. Moreover, it was stable in human liver microsome. From a safety viewpoint, it showed non-cytotoxic activity against hepatic cell and exhibited lower inhibitory activity against human MAO-A compared to linezolid. The potent antibacterial activity and all these improved drug-likeness properties and safety profile suggested that compound 14a-7 might be a promising drug candidate for further investigation.
Compound design guidelines for evading the efflux and permeation barriers of Escherichia coli with the oxazolidinone class of antibacterials: Test case for a general approach to improving whole cell Gram-negative activity
Spaulding, Andrew,Takrouri, Khuloud,Mahalingam, Pornachandran,Cleary, Dillon C.,Cooper, Harold D.,Zucchi, Paola,Tear, Westley,Koleva, Bilyana,Beuning, Penny J.,Hirsch, Elizabeth B.,Aggen, James B.
supporting information, p. 5310 - 5321 (2017/11/13)
Previously we reported the results from an effort to improve Gram-negative antibacterial activity in the oxazolidinone class of antibiotics via a systematic medicinal chemistry campaign focused entirely on C-ring modifications. In that series we set about testing if the efflux and permeation barriers intrinsic to the outer membrane of Escherichia coli could be rationally overcome by designing analogs to reside in specific property limits associated with Gram-negative activity: i) low MW (7.4 1), and iii) zwitterionic character at pH 7.4. Indeed, we observed that only analogs residing within these limits were able to overcome these barriers. Herein we report the results from a parallel effort where we explored structural changes throughout all three rings in the scaffold for the same purpose. Compounds were tested against a diagnostic MIC panel of Escherichia coli and Staphylococcus aureus strains to determine the impact of combining structural modifications in overcoming the OM barriers and in bridging the potency gap between the species. The results demonstrated that distributing the charge-carrying moieties across two rings was also beneficial for avoidance of the outer membrane barriers. Importantly, analysis of the structure-permeation relationship (SPR) obtained from this and the prior study indicated that in addition to MW, polarity, and zwitterionic character, having ≤4 rotatable bonds is also associated with evasion of the OM barriers. These combined results provide the medicinal chemist with a framework and strategy for overcoming the OM barriers in GNB in antibacterial drug discovery efforts.
NOVEL OXAZOLIDINONE DERIVATIVE AND MEDICAL COMPOSITION CONTAINING SAME
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, (2014/07/08)
Disclosed is a novel oxazolidinone derivative represented by Formula 1 above, in particular, a novel oxazolidinone compound having a cyclic amidoxime or cyclic amidrazone group. In Formula 1, R and Q are the same as defined in the detailed description. In addition, disclosed is a pharmaceutical composition for an antibiotic which includes the novel oxazolidinone derivative of Formula 1, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. The novel oxazolidinone derivative, the prodrug thereof, the hydrate thereof, the solvate thereof, the isomer thereof, and the pharmaceutically acceptable salt thereof have broad antibacterial spectrum against resistant bacteria, low toxicity and strong antibacterial effects against Gram-positive and Gram-negative bacteria and thus may be effectively used as antibiotics.
BIARYL HETEROCYCLE SUBSTITUTED OXAZOLIDINON ANTIBACTERIAL DRUG
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Paragraph 0088; 0089, (2014/08/19)
The present invention relates to a biaryl heterocycle substituted oxazolidinone antibacterials shown by general formula (I), a pharmaceutically acceptable salt thereof, an isomer or a prodrug thereof, wherein R1, R2, R3, R4, R5, A and B are as defined in the description. The present invention further relates to a method for preparing the compound, a pharmaceutical composition and a pharmaceutical formulation comprising the compound, and a use of the compound in the manufacture of a medicament for the treatment and/or prevention of infectious diseases and a use for the treatment and/or prevention of infectious diseases.
OXAZOLIDINONE ANTIBIOTICS CONTAINING FUSED RING
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Paragraph 0099; 0100, (2014/08/19)
The present invention relates to a fused ring-containing oxazolidinone compound shown by general formula (I), a pharmaceutically acceptable salt thereof and a stereoisomer thereof, wherein R1, R2, R3, R4, R5, R6, A, B and C are as defined in the description. The present invention further relates to a method for preparing the compound, a pharmaceutical composition and a pharmaceutical formulation comprising the compound, and a use of the compound for the manufacture of a medicament for the treatment and/or prevention of infectious diseases and a use for the treatment and/or prevention of infectious diseases.
BIARYL HETEROCYCLE SUBSTITUTED OXAZOLIDINONE ANTIBACTERIAL AGENTS
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Paragraph 0184; 0185, (2014/09/03)
The present invention relates to a biaryl heterocycle substituted oxazolidinone antibacterials shown by general formula (I), a pharmaceutically acceptable salt thereof, an isomer or a prodrug thereof, wherein R1, R2, R3, R4, R5, A and B are as defined in the description. The present invention further relates to a method for preparing the compound, a pharmaceutical composition and a pharmaceutical formulation comprising the compound, and a use of the compound in the manufacture of a medicament for the treatment and/or prevention of infectious diseases and a use for the treatment and/or prevention of infectious diseases.
FUSED RING-CONTAINING OXAZOLIDINONES ANTIBIOTICS
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Paragraph 0181; 0182, (2014/09/03)
The present invention relates to a fused ring-containing oxazolidinone compound shown by general formula (I), a pharmaceutically acceptable salt thereof and a stereoisomer thereof, wherein R1, R2, R3, R4, R5, R6, A, B and C are as defined in the description. The present invention further relates to a method for preparing the compound, a pharmaceutical composition and a pharmaceutical formulation comprising the compound, and a use of the compound for the manufacture of a medicament for the treatment and/or prevention of infectious diseases and a use for the treatment and/or prevention of infectious diseases.
NOVEL OXAZOLIDINONE DERIVATIVE AND MEDICAL COMPOSITION CONTAINING SAME
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Paragraph 0190, (2014/02/16)
Disclosed is a novel oxazolidinone derivative represented by Formula 1 above, in particular, a novel oxazolidinone compound having a cyclic amidoxime or cyclic amidrazone group. In Formula 1, R and Q are the same as defined in the detailed description. In addition, disclosed is a pharmaceutical composition for an antibiotic which includes the novel oxazolidinone derivative of Formula 1, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. The novel oxazolidinone derivative, the prodrug thereof, the hydrate thereof, the solvate thereof, the isomer thereof, and the pharmaceutically acceptable salt thereof have broad antibacterial spectrum against resistant bacteria, low toxicity and strong antibacterial effects against Gram-positive and Gram-negative bacteria and thus may be effectively used as antibiotics.
