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

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.

SUBMITTER: Zhao H 

PROVIDER: S-EPMC5430409 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature