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Synthesis and β-Lactamase Inhibition Activity of Imidates of Diazabicyclooctane

Abstract

A series of new imidate derivatives of avibactam (diazabicyclooctane derivative) was prepared for their prospective β-lactamase inhibition activity. The compounds (VIIam) were prepared through multiple synthetic steps; starting from benzyl deprotection in cyano derivative of diazabicyclooctane, sulfonation of hydroxy intermediate, and late-stage modification at C2 of the bicyclic ring to form the final compounds. The compounds were subjected to antimicrobial activity alone, as well as a combination with imipenem against ten bacterial strains expressing variable β-lactamase(s). All the compounds did not show bactericidal behavior when tested alone, however all compounds minimized the MIC value of imipenem indicating their β-lactamase inhibition strength, in vitro. Four compounds showed highest activity (MIC \( \leqslant \) 0.125 mg/L), and comparable to avibactam against six bacterial species.

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ACKNOWLEDGMENTS

Ministry of Science and Technology, P.R. China is gratefully Acknowledged for the award of foreign expert program to Dr. Haikang Yang and Dr. Zafar Iqbal.

Funding

This work was supported by the grant from Science and Technology Department of Ningxia, P.R. China (no. 2018BCG01001).

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Correspondence to Zafar Iqbal or Zhixiang Yang.

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The article does not contain any studies involving animal or human participants performed by any of the authors.

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The authors declare that they have no conflicts of interest.

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Lijuan Zhai, Sun, J., Ji, J. et al. Synthesis and β-Lactamase Inhibition Activity of Imidates of Diazabicyclooctane. Russ J Bioorg Chem 48, 1059–1067 (2022). https://doi.org/10.1134/S1068162022050120

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Keywords:

  • diazabicyclooctane
  • imidates
  • antibacterial activity
  • β-lactamase inhibitor
  • avibactam