Identification of Better Pharmacokinetic Benzothiazinone Derivatives as New Antitubercular Agents
| Autor: | Yun Chai, Bo Wang, Guocheng Huang, Kai Lv, Mingliang Liu, Bin Wang, Apeng Wang, Xuefu You, Yu Lu, Zengquan Wei |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Drug Trifluoromethyl Drug discovery Stereochemistry media_common.quotation_subject Organic Chemistry Biochemistry 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology chemistry Pharmacokinetics Drug Discovery Aqueous solubility Mycobacterium tuberculosis H37Rv Moiety media_common |
| Zdroj: | ACS Medicinal Chemistry Letters. 8:636-641 |
| ISSN: | 1948-5875 |
| DOI: | 10.1021/acsmedchemlett.7b00106 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|