Discovery of Fluorine-Containing Benzoxazinyl-oxazolidinones for the Treatment of Multidrug Resistant Tuberculosis

ACS Medicinal Chemistry Letters
Hongyi ZhaoHaihong Huang

Abstract

A novel series of fluorine-containing benzoxazinyl-oxazolidinones were designed and synthesized as antidrug-resistant tuberculosis agents possessing good activity and improved pharmacokinetic profiles. Compound 21 exhibited not only outstanding in vitro activity with a MIC value of 0.25-0.50 μg/mL against drug-susceptible H37Rv strain and two clinically isolated drug-resistant Mycobacterium tuberculosis strains, but also acceptable in vitro ADME/T properties. Moreover, this compound displayed excellent mouse pharmacokinetic profiles with an oral bioavailability of 102% and a longer elimination half-life of 4.22 h, thereby supporting further optimization and development of this promising lead series.

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Citations

Apr 1, 2018·ChemMedChem·Pankaj Kumar Singh, Om Silakari
Jul 25, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Claudia FotiOttavia Giuffrè
Jul 15, 2021·Journal of Medicinal Chemistry·Qianqian ZhaoWenqiang Cao
Aug 17, 2021·Antimicrobial Agents and Chemotherapy·Shaochen GuoYu Lu
Nov 23, 2021·The Journal of Organic Chemistry·Lindsey G DeRattScott D Kuduk

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