2. Academic Validation
  3. Discovery of Fluorine-Containing Benzoxazinyl-oxazolidinones for the Treatment of Multidrug Resistant Tuberculosis

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

  • ACS Med Chem Lett. 2017 Apr 12;8(5):533-537. doi: 10.1021/acsmedchemlett.7b00068.
Hongyi Zhao 1 2,  Yu Lu 3,  Li Sheng 1,  Zishuo Yuan 1,  Bin Wang 3,  Weiping Wang 1,  Yan Li 1,  Chen Ma 1,  Xiaoliang Wang 1,  Dongfeng Zhang 1 2,  Haihong Huang 1 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing 100050, China.
  • 2 Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing 100050, China.
  • 3 Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China.
PMID: 28523106 DOI: 10.1021/acsmedchemlett.7b00068
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.

Keywords

Antitubercular agents; drug-resistant tuberculosis (DR-TB); fluoro-benzoxazinyl-oxazolidinones; structure−activity relationships.

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