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 activity (MIC< 0.15 μM) against the drug susceptive H37Rv strain and two clinically isolated multidrug-resistant strains. Compounds and 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.

No abstract

A series of 8-nitro-6-(trifluoromethyl)-1,3-benzothiazin-4-ones (BTZs) bearing an oximido or amino nitrogen heterocycle moiety through modifications at the C-2 position of BTZ043 and BPTZ169 were designed and synthesized as new antitubercular agents.