2. Academic Validation
  3. Identification of Better Pharmacokinetic Benzothiazinone Derivatives as New Antitubercular Agents

Identification of Better Pharmacokinetic Benzothiazinone Derivatives as New Antitubercular Agents

  • ACS Med Chem Lett. 2017 May 10;8(6):636-641. doi: 10.1021/acsmedchemlett.7b00106.
Kai Lv 1,  Xuefu You 1,  Bin Wang 2,  Zengquan Wei 3,  Yun Chai 1,  Bo Wang 1,  Apeng Wang 1,  Guocheng Huang 1,  Mingliang Liu 1,  Yu Lu 2
Affiliations

Affiliations

  • 1 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • 2 Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing ChestHospital, Capital Medical University, Beijing 101149, China.
  • 3 Tianjin Chase Sun Pharmaceutical Co. Ltd., Tianjin 301700, China.
PMID: 28626525 DOI: 10.1021/acsmedchemlett.7b00106
Abstract

A series of new 8-nitro-6-(trifluoromethyl)-1,3-benzothiazin-4-one(BTZ) derivatives containing a C-2 nitrogen spiro-heterocycle moiety based on the structures of BTZ candidates BTZ043 and PBTZ169 were designed and synthesized as new antitubercular agents. Many of them were found to have excellent in vitro activity (MIC < 0.15 μM) against the drug susceptive Mycobacterium tuberculosis H37Rv strain and two clinically isolated multidrug-resistant strains. Compounds 11l and 11m display acceptable safety, greater aqueous solubility, and better pharmacokinetic profiles than PBTZ169, suggesting their promising potential to be lead compounds for future antitubercular drug discovery.

Keywords

Antitubercular agents; benzothiazinones; pharmacokinetics; spiro-heterocycles; structure−activity relationships.

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