Antibacterial oxazolidinone analogues having a N-hydroxyacetyl-substituted seven-membered [1,2,5]triazepane or [1,2,5]oxadiazepane C-ring unit

Suzuki, Hideyuki; Utsunomiya, Iwao; Shudo, Koichi; Fukuhara, Norio; Iwaki, Tsutomu; Yasukata, Tatsuro

doi:10.1016/j.ejmech.2013.03.003

Cited by 16 publications

(8 citation statements)

References 49 publications

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“…Oxazolidinones such as MRX-1 developed by MicuRx Pharmaceuticals and LCB01-037 developed by LegoChem Biosciences are currently undergoing the phase III and phase II clinical trials, respectively. Of late, research on oxazolidinone antibacterials is focused on overcoming the linezolid-resistance, broadening of antibacterial spectrum against Gram-negative strains, − exploring the utility in diseases of central nervous system (CNS), and reducing the toxic side effects . To achieve these objectives, extensive structural modification of oxazolidinone pharmacophore has been done.…”

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confidence: 99%

Design, Synthesis, and Antibacterial Evaluation of Oxazolidinones with Fused Heterocyclic C-Ring Substructure

Deshmukh

Jain

2017

ACS Med. Chem. Lett.

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A series of novel oxazolidinone antibacterials with diverse fused heteroaryl C-rings bearing hydrogen bond donor and hydrogen bond acceptor functionalities were designed and synthesized. The compound with benzoxazinone C-ring substructure () exhibited superior activity compared to linezolid against a panel of Gram-positive and Gram-negative bacteria. Structural modifications at C5-side chain of resulted in identification of several potent compounds (, ,, and ). Selected compounds and showed very good microsomal stability and no CYP liability, thus clearing preliminary safety hurdles. A docking model of binding to 23S rRNA suggested that the increased potency of is due to additional ligand-receptor interaction.

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confidence: 99%

Design, Synthesis, and Antibacterial Evaluation of Oxazolidinones with Fused Heterocyclic C-Ring Substructure

Deshmukh

Jain

2017

ACS Med. Chem. Lett.

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“…in 2013 synthesized a series of oxazolidinone analogs bearing a N ‐hydroxyacetyl‐substituted [1,2,5]triazepane 141 or [1,2,5]oxadiazepane C‐ring unit 142 as homologues of an earlier drug candidate eperezolid. Several of triazepane derivatives exhibited potent in vitro antibacterial activities toward not only Gram‐positive but also Gram‐negative and linezolid‐resistant pathogens (Scheme ) …”

Section: Discussionmentioning

confidence: 99%

Overview on Developed Synthesis Methods of Triazepane Heterocycles

Zeydi

2017

J Chinese Chemical Soc

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Triazepanes are important seven‐membered heterocyclic compounds with nitrogen at different positions in the ring, and have many pharmaceutical activities. Compounds with the triazepane core have attracted much attention as a result of their interesting biological properties. A study of the literature shows that there are various methods for the preparation of triazepanes. In this review, we have classified the methods based on the nitrogen position in the final triazepine products into four triazepine classes, namely TAP‐1,2,3, TAP‐1,2,4, TAP‐1,2,5, and TAP‐1,3,5.

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“…15 In fact, eperezolid showed stronger antibacterial activity in vitro and better therapeutic efficacy in vivo than linezolid, 63 but due to concerns about the issues of its safety and human PK, linezolid was selected as the first choice for clinical applications as a candidate drug. 64 Suzuki et al 65 used [1,2,5] triazepane and [1,2,5] oxadiazepane to replace the piperazine ring in eperezolid to synthesize a series of oxazolidinone compounds (12a−d, 13a−d, 14a−d). These compounds exhibited high antibacterial potency against both Gram-positive bacteria and Gram-negative bacteria in vitro.…”

Section: Spiropyrimidinetrione Oxazolidinone Derivativesmentioning

confidence: 99%

Current Landscape and Future Perspective of Oxazolidinone Scaffolds Containing Antibacterial Drugs

et al. 2021

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The widespread use of antibiotics has made the problem of bacterial resistance increasingly serious, and the study of new drug-resistant bacteria has become the main direction of antibacterial drug research. Among antibiotics, the fully synthetic oxazolidinone antibacterial drugs linezolid and tedizolid have been successfully marketed and have achieved good clinical treatment effects. Oxazolidinone antibacterial drugs have good pharmacokinetic and pharmacodynamic characteristics and unique antibacterial mechanisms, and resistant bacteria are sensitive to them. This Perspective focuses on reviewing oxazolidinones based on the structural modification of linezolid and new potential oxazolidinone drugs in the past 10 years, mainly describing their structure, antibacterial activity, safety, druggability, and so on, and discusses their structure−activity relationships, providing insight into the reasonable design of safer and more potent oxazolidinone antibacterial drugs.

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Antibacterial oxazolidinone analogues having a N-hydroxyacetyl-substituted seven-membered [1,2,5]triazepane or [1,2,5]oxadiazepane C-ring unit

Cited by 16 publications

References 49 publications

Design, Synthesis, and Antibacterial Evaluation of Oxazolidinones with Fused Heterocyclic C-Ring Substructure

Design, Synthesis, and Antibacterial Evaluation of Oxazolidinones with Fused Heterocyclic C-Ring Substructure

Overview on Developed Synthesis Methods of Triazepane Heterocycles

Current Landscape and Future Perspective of Oxazolidinone Scaffolds Containing Antibacterial Drugs

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